Macromolecular fluctuation and biological function

Liquids, 42 (1989)

JoumlllofMdaucm

Elsevier &hncfi

c* Ssabb,

pub-

sanogyc

B.

of

Departmsrrt

m-70 Amatmhn-FMntedinTheNetherlande

B-V,

SD

s. Lbl&?wvich

and

BiopTplaics,

Ihzivereity

I&d&at

Suhoot

of

Dsbrocen,

H-PO18

Dt7breoen, Rungur#

The rlatulw and oontribution to bio20giaa2 ftmotion of nKzomnnotecuzQr fZuatuatCons are d~cuesedatphunomsnotogZuuZ tsvttt, !l'haprot&n@uotuations inunz~jknction, thu Zatu~tundrotat&mat nwbiZ5t.y ofint3wmemb=s prottzins Qlw treated QS asssntiaZ tzw
*A

bioZogicat

5uatXon8

arw?

mm

to

ikWUh3

biozogicclZquastlzon

to unsunr

in tha fauwtionaZ

oxi&

of tha

statcament, dpamiumotion8

gioat

8~stems

mqj

of fhatuations

t&m

con~t~a

to

tiuat ftuatuutions FLuotuatSon uwq2Zsx

in

m&n

f&ma

more

or

pkp83c8

Zn

tha

pio08e0ond.s

/<.B_

compt&ated

btiiZt

preciscrtu

Ztw8

rt?tatdV8t~

or

bg

into

to

bast

SqxWimSntiZ

ones

are

not

uan l/As

a widu

&

appZ@zg som~

apPruMohS8,

the

the

6magme-aubstzwta

ts,

mag

of

thess

th

Amoq

Tlatringstutis-

an

fun

dizwut

th

speciatposStion-

of

th

fo?

!7%e t&e

is that of

a

have

time

motion8

tatinoZo~

atthough

~&?roCohS,

tzasiZu avai&zbzS

tha

of possGXZi-

tuveZ

occup~a

some

of

a roZo jhnn

fknatian.

moL~~Zas

part

the

aZear

phsias-

comprbSn

sScond8~

ruikvunt

auhie~a

vurie~

bas%c

studiad

a8

@UC-

ths

supximotsauZarZnkZo-

proteins

the

membzwna

b#

But

ofstut&tiCaZ

protein,

s6vsrrrZ

dusarCbttd

have

Laus

qldantwn-biooh&tm/*

Sim&dS

mf_

Tha most

act&ii+

structurs,

BpolltWUOUS

@uctuat&na /aaa

ZavoZs

tht3 confoz37nxtZon of

aotution

that

to tha bikZogica2

sxpertmsnttztZ~/

in the
bGXi&

oquilibriwn.

inmoZtzcadarao0tzZtas

bSoZogXoa2

and

43Imzt

u~ZZ.~

gwamsdbythe

thtxor&ioaZZ~

U

contributa

at differunt

intramotacutarmotion, /both

i%ting

potantiaZ2~

&maSns

8UCh

themo&namiu

lriZZ be whethur

abovs

to

?h

t3zpaatsd near

be

of

nxzJoriQ

Can

h?

statisticaL

studisd

be

Czo-

of

obsemrations

through ths

of

rnor6

weti-

nentuZista. &q/d

danoa

the

?WltIrOU~

thut rapidfluctuationara

LZndersMm-w maad

t:h%OlWtiCQt

and the

his

theoret
0167-7322/89/so3_60

Q

basiopropartilas

carorkers and

in

th%

uqxwzinsnta2

SO-Se

data

of

first

the

/ref.

pmtainswa 8/_

obtainad

1989EleevierSciencePublinhers B-V_

ezparimentat

Maryl

80

evil

fowfabu good

fe>

2yW~eWs fhnn

thu

mid-sevmtias

tit2

tha mid

Houtrvur, a cunphx and

aZs0

8upramoteuuZur

uompZecity

of the

bioZogica2

studied

roZs

in raZatLon

&

toric uffautor/

induaed

geatad

at

give

Monad

to anspe

at

t?m

of KoshZund

quita

/8aa ref. protein

/ref.

time domaine

oontributing

~a attumpt

otassification

of

ths msdZator

uminentt~ snqma

protein

16-2&l/_ NaturoZZ~,

aupposerr a wide aa

thsilr far more

to euggast

a

time

that

hetp

domain

had been

sug-

modet

this

as

/MEXM/ aon-

invotvewnent

of fZuatuat2on

to

comptZcated

tha

cu*~Z~~;Sc

reguZation_

- biotogicat

ph&caZ

Cazwri,

intaxwutsona

vatitjj

wett

bu

possibtu

@z&ion

in ths und&rstanding,

ZooseZg dufinad

16/,

kinatiu the

aZZos-

/ref_

tham

of

raguta-

/s-g_

unv&wmnentut

to tha binding

might

mnong

bean

aoctz+td

the aZZosterSc

dusaription

and

mentioning

this

or

ZsvsZ

has

and fZuctumG.ona

Our moZecuZar

action

nature,

fZuatuations

authors

/refs.

together

avan

rtzZaCion of f2uctuations and

kcat

in anqnm

not of twuQfmss, Hurtwith

ths

73/

tzwnaittons

fZu&uattin

Zavttt of puttorn

3/.

at the moZecuZar

Sucoc~esfit and wideZu

the-4

a few

intar-

ZweZ

I6/ detaZt with

of statistiuaz

0ffZuctuuthm

poO6w

high

ints=ctiona_

statistiua2

fin&ion.

stabolulta mathamaticat-phyaicat

directty

the

and a genezwZ%sad

intsrustZuZar

ran&m

prussnts

the

to

in intxwnoZacuZar,

ftuctzuztiona

their

G&ton

of

in m~Z~arZar

dus

overview

-a

-PasstZa cmd un

maid@

the moZuuuZar

et at. /ref_

indtzptzndantt~ h

tributxon

nwtiona

miasin~

and aZso

confomrationa'l

invoZvamant

&namic

Q brief

motions,

despite

thttorias firmr tha induaad-fit

l%s direct

to

that d@zamic

tion eZabo=tod

of

i8

ofmoZaouZar

fhctuations

jknctions

muinZM

rote

intraceLZuZur

motions,

The possibiZi_ hcva

3-12/.

tho

we attanpt

paper

intxumembm,

Dpantic

1.

of

a~sttmm_

of the bioZo&cuZ

motscutar,

/rafs.

or carZtuZ4z.rZaveZs

Zattsr

In thG9 short concept

8O-e~

approaah

cor-

inttwpratation

propar-

of

bioZogicaZ

macromozecuz6s: Frc*n tha

7. rasponaibta moZoouZur/ AZZostaric

for

statistioat

Witions states

a.

!l%us coutd

to second

the

gene

prouassas

regions The

of

fZuctuatCons

protsin

not

inuZzLed,

since

/or

in pnemt

mctiona

in that

couZd

and

case

macro-

rttguZabitiQ_

difftwunt

uonfor-

tmnsition

jlwm of

ens

purtCauZur

ftuctuations

in

aonfolrnation

to

StseZf, fhh

pa

tima 2ulnges. may

hoZd for

dttpand

upon

DiJA-prot&n tha

intern&ions_

avaitabitiw-tims_inttzrvaZ

Tha

gena of

aoti-

certain

in the ohromatin_

xwguZutoqf

be

rrfaatBrfZuotuution8.

u differrrnt cZusa

Zonger

mag

dtitribution

scate

different

aZZosteriu

or even

tima

having

their

rapresent

nanosscond

atatoe are

have

A sim-iZar cutegom vation

to tho

aonformationat

mationat

another

pioo-

aottviQ

of certain

DNA binding

nuaZtzar onoogene

products

61

is such uticiting

that

miZd

asZZuZur

ovtzmZt

Zu un iqortant stitt

roZu

prasent

in

ahangus

Tha

rtmpomims,

in katzping oeZZs

in wZZ-dutaotubZa

sacrbd, unpbtished

conaentmtior_

thair

qa

pmtuin,

tn pmZifemtivs

qwmtitSas

obaeruuti~/_

to

SB%ln

after

~ouever,

u-g_,

hzaving most

state

/ass

texminat

shifting

suffcaia.nt for

btit

tikeia

ref_'81/,

diffaruntiut&m

the diatributGn

/G_

ofpoten-

mmfolnntxblazstatus bg phosphorIjZatiu?l aodd zal.pu2$facmtributt3 toafinding of certain nuctuar oncqptnu poduats to aaah other cog%ml jlanction. /ZZka SV40 T to ~63, ElA to Rb, fos to AFI, sea rufs, 22, 23/ are axcanpZus of tiuz

attostm-io A that

int4motZon8

the

motions

gZ~aopwte&za

rastriatad

transmembzwno

oiaticm

and

by

even

axwna

moZ6wzaiL9s aZZ

havs

T?uz

shown

,2uctuation


titt

mtzmbnme

aaaassCbiZitg

of

txvmsmambxwna minutu

em6

tm*ion

of

othezr aithur

motiona

hama

vast who

~a

and

not

asao-

surfabe

pat-

/refa.

24,

Z6veZ_

tRv6Z

aompattnzt

inmwze

Of@uC-

86/ pm-

Soon

struuturaZZ~,

into

acaount

disousrrod

0mpZttx

and4avours


fXetd

to

taku

suuh of

as

it WS

or

6

rustriatud

poss%iZ5tio~

new

steps

anuZgsi8

ScuZa.

in.

imxzstigutiuna

in th&t

new &Zd

prots3n

wzth

of the pmtsin rtzaattin

in&wed

in

fauna

raaaZed

psripherat

of ionophorua

thiots

pattern.

28/ of the affeot

of auZZ membranes_

have

non-panatmting

butm

thioZ

of

Z~lmpho-

tmd monoaZofound

markurs

ionophoms

on

tha

cmd

the

surface

thioZ

aZttwing tuposur~

a dspe&7enatz on the attmosZZuZur bind
Tha

.tifferema8 apaatzwphotietti ttmt

an anhrrncad cstt

SGniZarQf,

mambran~

et at, /raf_ struotura

and abeencs

aacassibts

The ufftzct 87-d

cat&ma_

ovaraZZ

su ZfJIz/dqZ groups

-Zing

thioZ-DTNB

tn tho plasma

br, Batis

th

tha prasenco

a few &

mob
given

upon

swfuca

gotcnttit

thu

Zimitad

-Za

0nZy

PAGE

.;leacuramant

a

potentiuZ

dtztmnstmtad

subsaquunt

we

/and

and

13as inv,setCgatad

QB

tip&is,

i_tz_ a atzrtuin sort modat

h

j?rom J-IS

th6msmblvms for

at the mambzwnu

%andom*

of

Hed/,

of osZZ

antibod~se_

asZZs

of

of COZZ

target

m&urns

aaah

Gzducsd

oacur

ba rewrded_

An interesting

naZ

upon

a

dannrim,

mobiZiQ

an&o&

.i;oticuZar associationa

catsa

t&m

moZucuZar

QQCS

and

mot&n

a?zangua

to present

or

nxq

ZMtud

/rtxfs_ 28, 27/_

rmtmk

aortaint~

of ptaenm

order

moaaio

thu man&me

foresean

h’

structza-tzs,

Those

inftuarwod

Thtz fZip-j%q

fluid

wgs

nmmbrarms_

motacutas

acaZe_

ths~rpdtiadar

these

ac@opzaamM

bioikgic~2

or eq.nw8sionofnswgenssat

in

aZameznt8 dapsnd

If z.m take

the

tima

of reasptor

antigena

or Cn both

in

gxwd<'snta or surfaatz ahargtw,

Si~e~A?&Ohmn

that muq

couZd

mtnuta

the unrestrioted

tionaZZ#

Zip&is

s urnxuzding

aignaZ%ng of

scr3bad

tha

dissoaiat5on

or procssaing

tuatiO?L

and

aZactzwchtuniaaZ

sttaond or

turn,

*ortance.

~~rtIlpooffZuotuat~havingBnormowr~ZogiwtimpoFtancs~

of

tiZZ

of aruuXa2

tha nunwcZonaZ

tha

on thtz conaen-

antibo&'OKT-3,

62 directed

againet

tion-dependent earzg

compZaxee

increas36 of

be

d&placements

coupZad

to

Kthout

going

qtee-

it ti easy tentie

w

change

maxmorata

the

panied

br/ the mcmentoq

ttctes

in both

and

whiah

those

of

of membrune qon

in

tike

tJz% whotu rin A,

oppeamnce

dqotarization

or

o%ZZ.

An uxomp2e

and

t+mUS

in

CpZoaporin

A on

meohanism

of

to provide

the

be observed Fkgocutssis axrrenta.

in a reverse bH

human

to

humun

rmarophages

of

inizct

bg

aontinuou s

c%ZZe

membmne situution,

macmphages technique and

currents

aoincicEng

membrane

the

ia

fillnZ2g

ac&antage potent&Z Ince

than and

sing26

The phagou~toeis observation.

a&it&n

of of

that

a

as ~22

ThZe

effect

of

of repta-

cou2d

be

fast

con

QZSO

35/ reported

that

reaponees. struoture

/ref. chungas

in

ionCa

Zag

a?mnneZ

~a% appZZ%d ionic

Zatez part&tee a

other

a waight-

sort

aonfigwtion

After

as mouse mmq

aeteativu

tranememb~e of

in organ

represent

shwur

h

Qa2oepo-

doss-dependent

to have

membrane

ti aacompanied

sig-

the reaponeu

intsmatione

and coworkers

of

p~&togic

pxxiuced

30-341,

in the ceZZ-attached aatlvitu

hightydepends

indiapensabts

cuusing

/refe.

that mobiZity

showing

may

cm&-

observation

upon

knam

effeat

mem-

upon

t?Ke

Zynphoc@ss

thSs drug

aeZZ-enyiromnont

vidao-micmacopiuut

attaahmant,

bZood

sateotion

tx18 measured.

purticte

periphemt

response,

the gresmtic

reguZats

re jeotion,

imputse_

par-

mcrflhave

become

CntervaZs

intmmembrune

dependent

b.y us

that

time

auawn-

perturbutiaa

gimm

envi-

map/ be

Both

q

to

PO_

p-ieaes of Tor-

membmna

aZZogm,$X

c%lZ-csZZ,

between

Rztch-aZump

~8

discussione, membrane

suggest

and

FZllmphocUtas

a better

of

z2/mpho-

nerva

2arge

ZikeZg

the

in

impuZs%

etrict2~

potentiut

tapa

thie ear2u

a2Z

of

ofthe

Atthough

-totoxic

Retotionehip

I.

of hwm

the over

of an

Zeaftete

to

are

of

I m3

Zmhoc&es,

antibiotic,

suppressfng

on 0622 metobo2Zem,

ing factor

enough

of this

Z~hoC@~Se

eing2e

a

~%rpoZarisation,

endecapeptide for

at

of

thepZan%

m&M68

or

ama

-ID@C,

was

J?8/ with

%quiZibrium

e-urface etements

newwtranentitters.

p2asnaa membm6

~emblrzne depolarization

tow

/ref_

Of

a cucZic

e'fsota

partictas of

potentiuz

studied

trsnemie aion

und externat

reZ%ass

3-f3~OIWJ#3s

at

passage

aa

events

fluatuatione

291

concs*ttra-

interpreted

Zogicat-sounding

of a ?opuZatZon

observed

st a2.

the

tmspZantatims

8pZ%m

czyof+ixed

wers

These

~822

/ref_

eZementaperpendi.cuZarto

changes

pmteine,

a2though

that

data

in a

the uonfo~tiona2

important

the

showed

the

Ba2dsm

ni,nicarxta- ThM?, drmse,

of

the protop2asmic

atlowed

The

metiboZiem-dep%ndent

organ,

The ruunbur of the

tions

in

re%uZted

t lWnallltlRlb~

far-reaching

after

=Srease-fiurcture r%pZioaa

bmne,

the

MClZZer et aL

and

eurface,

membrane


expoeure

eZeat&a

during

chwzgea

certuin

into

aeZZ

aacossibiZit~_

changes

intemationa.

before,

tti2

to inxzgine that

rmmtenta2 pedo

of

the

in the

causing

m%mbxYInu 0ffeats,

vortiuaZ to

T3

period

ahurv1%2%

tlc1astudied foZZ&ng

snhancodimJardandoutwluitimo_~tsing~aharmez with partiuto

enguZ,3nsnt tsere observed.

The ftorotion-asso-

oiatid

channe2

Gannet,

again

Zar ZeveZ thu

aativiw,

n 0f Batis pot&iuZ

kkmbmno

thta

in

ao-caZZad

uoZZa_

time r47vaaLing

eukav0lw

aasu

amount

the=

stru0tauwt

tha

being

s+udiss of data of

of

8Q/ where

0ndfknctSo-

42xcitabZa coZZ8,

a c0nneution

gu&raZZy

ion

A very

in COZZS

palv~ZZsZa

of

the

in a aonsi&r-

bstx&iwn ahann

findings

o?ua cs3tz twa:

of'

throughappZiw-

cotlected

of these

i-s_

in casa

aacapted_

&cmneZa

have bmn

inters8ttng

&¶ 0nZu

it aupptamanto /raf_

has betzndevatopad

aysttzm. On tha bcs50

that

of

ia _Far from

a nwnbur

nervous

to auggaot

~1s might

avsn

th% tzzcitabza onu

/soa

36, 3?/_

FZuorescenco Of

Ens~

l!wnafer

3-72/

enuw

/FRET/.

itar fluotuatX0n8 intrammbmmtz Ziving

FrobZem

of

of indivi&uZ

ot

aonunue

ansrylll tmnefsr on

a

Steinberg chuin

atmZ2

pubZishad

moZsoutss

snergy

tha appZ&xabiZi%

rasutts

anew

ad rather J*er over

thtzoruticaZ

FBratar--6

mstZty

Zattar

39/. A racunt

Rii-ass on

puper

protuin

to appty

T

t2umsfur

short

that

as predtited

diatancas

studios

the

Fdrstar

tho

matrix.

I' intmoZe0uZar

in

tEsrmaZZu

at_

of

hSgh

and Of

azcitation

40/ confimd FRET

and oaZmodu-

ftuctuations

/rtzf_ 38/_

an cnomuZousZy

It ~~1s

Kaaa

ftuctuation.

tmruzferrin

Hmvur,

re-

-es

officzkncy

indkcad et

wpe

Indezpandtznttg

oJ2 ths enCronmsnt.

has sham

stud&ng

ovarcan~~

of O'licrw ot aZ_ /ref.

bg 5wowi

to thtz nature

for

of protsin


ws

resonank

aeZZs.

_-Xuatuation

pqwr

author8

ftuotuatia

upptication

a method

5s

method

intmZtwu-

pmtsina,

,f0r indiract

uatiow JfZ:czf

bu

demonstratad

insansitiva vaw

to0aZ

moZt~uZa,

monitored

ux&angu

uanpstant

of the Fn'%T a8 a rnecLsxra of intlmnoZtwuZar

to stu&

T&sir

craaae

as

tlurnafer /iwf-

1~3s appZied Zin_

a

&veZcped

to studg

tznz~

Gis

of 85wpZe

/38/

fuU

hurtz, the

i-o_

cgtomatrlj_

at.

a

quite

maarm~L3zuta8,

variab
In 198G Somo&

bg

'IH-aIH

oartg

hua bstxn a_ppZiad for stu&ing

rotationships,

~JJ ftow

the

mant
This method

indivi&aZ

since

revieszd

wii?Z be

pxwzimitg catts,

invented

extensivsZz/

oniCE/ one

tran8far

tasted

as a t,lsas?+l-s of FZuotuation

the nrang technSquas

Lindersttim-Lung

/refs.

in

to aaaompang in

K"

thtzmoZeou-

hand

et at.

as

structure,

of such

for

An impressive

MiZtor

recognition

ceZts

teohn~es

i-mnwm and

rufs.

structure

H*var,

On the other

28/ and

btosn

~y1a iduntifi*ed

&nantksat

the ooeraZtm~rane

tcwardssuuhgunelultization

patuh-ow

short

in the

mumbo

uaaa

that m8mbm-w

/ruf_

attsrad

nonuxuitabk

innnwze system.

of

the

step

of

st at.

changes

and muscZ0

Smportant

abZe

partieutar

rote.

p0ttzntiat 0hkmgerr ara

ohangas

t&n

this

undtzr2~ss tha po8sibiZi~

obs47-

nerve

in

has a~ttdtq%uzdfknctGnaZ

mambzwnu

naZ

which

do

These

in-

appoar-

anew

tm-

ttzmperoture

d-en-

dance_ A cuapZate2~

diffe-nt

tw

of

fZuotutztion

having

a faF

Zongar

corrsta-

04

tion

$imo

FRET

in

bond

Con A r6a6ptirs

u

aZeo

fZow

be anaZ~aed

qtonmbr

to

through rust

ths

Hmt?ver,

ihtina. case.

couZd

bg

atudg

than

Con A aZi$uots

6ffto&nc~

couZd

of tmsfey

of int_ZacuZar

at at.

/r6f.

41/

rai2ationships

prorcimity

Zab6Zing FRET

/.Ecpel+im6?z tuZ d6terminat&n

d6tatination

em.

with

not

uffi

and intermoZaauZar

th6

bbzd6run

m6mbrun6

ftuoresaein

and Ao-

b6

crictncg

appZi6d

d6tSFIITtn6d in 2s

routi?l62~

distanu6s

th6ir

ussd

in moZucuZur

for

qS-

turn /r6fl3. 42, 43/. l?maticaZZu of

th6

any

trunafer

batw66n

suitabla

city

th6

of

tuggsd

SUOp6, giaZda t6r the

not

vin

on

for

cot2

Zar w6ight submit

of

th6

and

sTit6

tha FCET

acn

tho

LatemZ

or with

which

however

c6ZZ

obtafnad

the absotuts

of

d&e&nod

bZood

93 kdatton

aZas6 tha

Th6

group

/r6f8.

of to

mat of Jo-

C@ametric affimLwyy

a

targa

th6 55 kduzton twight

I - aZuaa3 I and ctaas

tHmphoc#os

out

aott

intszmot6ouZar

r&or

Zut-

In o&r

tmnsfer

moZocuZar

so-uatted

the

much

/pZow

ovsr

a

four

ascmr&gZ~

thu

minut6a

and Con A r6c6ptor8,

recegtor,

the

of

in

in a.miuro-

v6q

method

within

so far

unGt and a

ba

w2th

c@am&ri.u

data

catt

poputation.

casa

in coZZaboration

fZow

adth6r

c6ZZ popuZution; couZd

in

out

a singZ6

epsuifi-

ant2bodias

variabiZi@.

an sntirs

6van

Th6

monocZonaZ

uarri6d

EoZogicaZ

of dutotin&tg

of the abov6

as

durmia

bs ctassifiad biotogioat

ataadu-atata

nature

a snapshot

of moZ6cuZos

and pot6ntiaZZE/

active,

can atqo

important

ba ju&sd

proximiw

surfuo66.

s-g.

mathod

mgasuremsnts

dG-

moZ6cugutat
IX - 0Zuss

histooompatibitiw

44-49;

SxbZZBa<

st aZ.,

in prass/.

proximi w

,functZonaZZu

a

dtitanuu

asZZ

ov6r

hQvs,

mtigsna

poriphamZ

raJcZecta th6 @zutGnaZZ~ C6ZZS,

of

of th6 who26

~-2 I? untG6n

11

on

msasur6mtznts

providing

Data

intartoukin-2

rELnanr mrtwwt. S&c6

aapabZ6

I - atass

in hwmxn

c6ZZ

&veZopad

Zllmphokina binding

11 and cuss cotqtaz

mozau

These

uvsmged

average

appt&ng

h6tsrogan6ity,

44-48/.

bstw64n

bu

auspona<~~,

l&I

baais

/refs.

for pair6

probZam

popuZnt~,

c6Zt-%weZZ

tanc6s

tha

of

Arndt-JovCn,

poputation

ZabeZ6.

distribution

!l+ansf6r, FcET/

a

aasursd

a singto

probZame

or tim6 deptznd6nt d6t6mrination

appZiwbZ6

suoh a6 c6ZZ

the rwm~~t

tha

and

EnargH

d&u

of

hmw@#luoua

bo

sffiai6nriaa

providss mttan

can

ovsrcan6

tmnsfsr

o36rcom6

is

donor-accsptor

ftuorczscant

ofcttZZs

can

at6ud&-stat6

ZubsZsd

ZabaZing

with

muttituda

knan~

sffiai6nq

exerts

struatur6

ua on6 of th6

ftuctuations.

of

Ming

a rostriot&m

manbras

6Z6m6nta

in of mmnbmxrmof ZZving ussfutmsthoda monitoring

Tht's statament

the m6asur6m6nts

of a fzuatuation

other

bacaus6

pattern,

on

i6

a gCv6n ths oth6r

vaZid

&-

proxGtiiq hand

tha

on sach othczr's fluctuation.

mobCZitl/ Ths

n;dma

ZatsmZ /r6f.

and SO/,

rotational! or

8imiZar

nwttins motiona

of proteins

within

parp6ndicuZar

to

th6 pZano-

that,

of the

control. manw

‘6fi

0aZZutar

andaZmostSt)~q

inznwwZu&cat

trmnoh~~hr mostI&

fh~twzti~~

the moZt7uuZar ndatias

t&n

in

on cotZ

and cmrkars

ZuZar

h%w

matrix

cuztured

patterns

on

thu

imnobiZ&atiun

the 0eZZa

higher,

stowed

down

the

~rtt ptatod Treatment protuoZ#5c changes

The

ZataraZ

the

the

ZmhobZastoid In contrast

ceZL

the

and

lO-foZd

uarZiar

of moat

than

tabetsd

0~22s

grown

matsriats

LMS

af

that w%th

I RHC antigens/

out a&oscaZatizb g@r

mambzune

thse

cntigms

intact

The

Bzmimts,

when

ceZZe

cuZtures_

cambination

/ref.

at.

of

cuZtura

S3/

fowxd

antsgans

imruasing

oeZ2

of

in B

dsnai~,

for

to sZo~&

,;LabtztCng02ass

tq that tabsted

antibo&

aartain

mambmns

or pro&h or

X MHC

lipid

Xntaot

an-

anaZo* antiboc&-

inwx&iZixmred in ths mmdun&Q_

cs m&rune

g dam

w3th

wara caZZ

of a

Thta rttsu2t-saru

proteins

Zipid,

thus

to high aeLZ avm

to

/ewnGzuntZ~

tikety

with-

d&naiw

trig-

ixmnobitiaation

of

by Aasodation ttznpo~

or psrmanent

forn;ation of bigger

astabtished

on thaaa probtams Xcoteon ataseia might

as rapCdZy

Zeading

tha

prottz-ine.

Function

oZtar

and

revaatsd

oonfluant

curtain st

in

tha dsnsiw of

histwoqxatibiti~

i&nticaZ

CrossZinkfzq

constraint.

prooaaeas

with

in suspancr~or_ at h+h

dif>%ae

antigens

13~18obtainud from

&em2

astr~aot-

thqf fowzdthatpmv63ntingmicroag~ga-

dr.te2lpretud that in the unporturbsc! aL&50 cZuse

effect

Fab _+qmunts

coa_*+ient

greator

the

%_~,f..oti.tienn-

slyrgasticme,

upon

photobtuaching

atso

aIv8s tinkdng

bI/ uppZ@zg

difmion

after

mrrtsriuZs deivad

upon

&%trar

and

agu

X.

SO/ and

dansiw

whun

thuae

thaip

d~~&tt/

cott

coztaot

mutrix

mambranes

I MHC pxwts2ns

bmnas

matrix

h

histocompatib
A similar

of proto minute

sugpstud

/mf_

of oat2

and

in-

24/_ Ths flznctionaZ sig-

5r,vostigated anttgena

mobiliiqj of o&zse

tion of the antibodies tigans,

CLuas

diffision,

abotiahtzd

Zatamt

tith

the

0autZuZur

anqmus

in

ws

of

mobititius

ia atso

of

rscovam

coZZ-aett

on axtmcsZtuEar of

on the infZuence

aZs0

awmmriaing

/f!r0m mi~~~seoond

motions

of @or

and

/r&f_ S2/,

/raf_

thu uffaata

interactions

motiZi*

h5ar and Edidin

fluoraecsnoo

a dgnificant

a

pattorn

of thus%

observad

Tha

Shch

rotationa

reprssant

ZatslulZ diffisson

j%brobtaats_

wa

and

S3/ reportad

61/,

ZctalvlE and

In&ptmdantZH

and Edidin

2nttxrcotZuZar

b8tm-z reviewed

of the msmbrane

dtxnsX_.

/mf_

diffi&on.

BQth

ae2tZ mtzmbxme

of mambmna

dapen&znue

/raf.

rsc%dZy

aspeats.

the

txxrnduation,

maotion

have

time acaZu/fZuotuatGn nificance

signat

incZuding

pmcsssos,

. .

/ref_ Gaper havs

Zack

compt4zxus q

f2urctione. EdZdZn ctaimcng

as/, show&g

ohich

that

mobili@ in a new

raoar,tZy presented

mttmbrunu

the

rueuZt

the fl;tid mosaic

~~2s aotuuttu

that

ovaramphasisad

c_~indapondent

heaviZy

;mtoina

Sndupar_?ant

ratting

mobiLi_

fluzction

or

an BlxletZent briaf

membrane

are

of caZZ ntembm

modeZ

upon

mot and

Fqe

of

noteand

and Edid
inmobiZizad qxitiat

Singur

can

entities, au-

of

66 ceZZ

surfact

ma&

in

motscutar3

tha

intomctia

70-68

tast

bs

obaexvsd

in

probtsms

flow

44,

aith6r

lqj this

that

Edidin,

48,

491.

0~

other

of

nqj

csZZ_

for

La,

tiona2

affi_nit~wnhanoer.

qumlnes. bik?ing

Tha zmg

invozving

Protein on

esnt,

of

UZZrCah

tith

prototyp6e

or

Kinasas

onas:

growth

6pid6mZ

with

Our knm?Zodgs through

pJwsptimZation

mcq

for

poesibZe Ths

t~wzmous

baaom6

faator

Zigand

modeZs,

ths M/C

and

/xvi-

aurfaas

a8

I of

ant.Ggancr ~XQ

servo

aa

a jknc-

pmat&aZ

of target

aomm-

otiented

trtmtmmta

or

hs im-

rn.w ahangu

&

w6ZZ

nnd

these

aap6ct

rsZated

subcZcsa~s

of

mzceptor

tho mucropha~e

of

Z+an.d dis6aSos

rsaqtor6 bH

compZ&aZg binding.

Zigand missing

Tha

of the racaptora

are

emmth

upon

cantmZ

j%Zd

is

to

_!m r6viaw9d

mcaptor

aoncerning

to ang hm

am

Yurpr6-

growth

fat-

/SF-I-R/

of

Bvokad obsuzm

tho

raasptors.

a&iviQi

also

a8

th6 confomm-

these

of

aoneequenoas

bindXng

h

wzdardanding

kinaao

with

at

dtitinguis%?

ths

fo-

aont
insutin-Zika

factor

b3ndXng about

Zigand

investigations

are

Quastions

aonfomtionaZ

of th4

oncogonsa. RTKB

/ECF+?/,

raepsatixZ~_

initiatad

Dis

/IW_?. 57/_

faator

ezach subcZass

is ahoat

AlHC ant+ma

probZmm_

a psz-Ging

mzccptor

three

growth

of

1

to

racttptor

evezn nclgativa infZuencing

aumpZ6z

aativatti.

2_/ Th6 MYC class

psptides

as

qZor6d

of idh% con&%x3

cZaa8

r6aoptors/

thaorsticat

binding

caZZ

tzz&1tanu6

aonaequnaos_

a$finitg

twr6

thsorstGzc?.

of particuZar high

T

ah

aeli? n~tunhmes

p roxzhtitg of MUG

insuZin

m&ho-

prox%miQ

caZZ-surface

in

betman

6xperi-

pro-vi&d

&OVS/

in

TX-CD3

ths

and

trtmsf6r

canpZ@x6a

Zimphokina

farr6aahing /a_~_

naarbu

68/,

/IGFI-R/

tmitimza

tra?mfer of

reZaticm0hips

funutionat

pxw&ntitiu8

in cas6

I_/

t~rosiruz kinaeas

/rsf_

for

E~.Js~*s

ani _FZuatuations

nuq

I*agLZator2/ proaosess

Zat6d

tha

tg

thoor6tiaaZ

lTE!7' /.66

?WL? zxzgs in rsaffptor piaarmacoZc~

r6a6ptor

tur raaaptor

tiomat

Of

b&ding

havs

&pmnias

mzesarch

dan and

ita

pxmotion

!.Qm&ne

aZ-

tU and

tlorsion of

important

aseo#iations

r;Ztarsd rscaptor-Zigand

Faaaptor

cusing

to

mq

opsn

pro&

pmximi

Tha

t?m

important

rsceptors

this

ideas

sty&

si@aZ

a_~_

8ptiaZ

Zigand

direct

Thee8

w622-dej%6d

441,

m%tkd,

and

an

affinitg

Zigand

to

us

methods,

ZikoZu

tmnsport

3_/

accumutating

ttlpe resmzana 6 6?luw

a ssZczctio?z advantapa

them

of rea6ptors

on

non-mmdtnn

/rof_

lVrat6r

Rmeptor

p2/aicaZ or

offers

start6d

th6 mod
non-mncbni~ed

murq/ spooifi_c rsceptors.

diq

tho

membrane

stu&fing

soaroh

antigczm th6

in

in

m6diut6Zv

h

that

2.42~62s. Uur

tha intsrhukin-2,

tha

atud%d

6nabZad

of

6mphas-taod and

tho ~622

C~I~VMZ~~&

48,

as

Deu

and

phmmmtma

of the %noun

at subpopulation

/r6fs_

SS/_

St?/_

in


or

couapping

54,

&?-R w8 CC280 ah-d

appziaation

dotogg

25,

rafs.

aZamta

/raf.

In th6 6arZp aan

on

of naar@

bZocking

m6ntaZ

/ime

i8

IW@L-

h

auto-

at pra-

smt.

zuss ia

Evbm

grrmth the

OF

fuatora, r%guzutio?l

of

impstus to

n6w

the

Conk-tbu~nofthap~strmc~toRTKflolctiononn~a~quateZ~ dsscribud%

uhanging

QppropriatS zwachas

sida

cDh?A cEolts and

dwuM

outZSnad

aZao

above,

be

Stu&

or certain

tine

th62uonsuquenc%a in

to

Zearn

how

szciting

faast

of

these

rea&lues

Zn

the

numsfeation.%SUapir

b#

corjunct%on

acid

with

the

moZoauZss

biop~e2uaZ

ara

methods

operzttedjZwnout-

andfrwnwithin.

Sari*

in ths dormin

suggust-7 that the

r6guZarzt&38

b5ndings

Time-=qoZvad

whZoh

e.g.,

phocN=,

of

Zacutes Z&at

auggast

different

Zibrium

bstweun

If

rs3qw?zas.

the driving

confommzSon8.

Tha

dif$erant

Xnvotve

other

growth

state

of

tore

the

t-ha

to affect

axyt~

of

a

Z+

to qtoske-

an

sharZd

mJ

aonsi&rud

of avaiZabtS

Zeast

just

ttqui-

aZZ-or-nono

be

mmp

at

t&n

were

ruoaptor

dandn

of

/raft.

showy

suggesting

that

rssponsras

bg uat

spoon on

dqunding

bu intBres:ing

a on

rather the

in

EGF-R

in

aortain

turn+ag

un

81/

target

if

the

wZZ

to

-captor,

tzn-

of

Zigand beWe=

thu

mqf c.zZso

estura

of

the

peptids

aonfolmationaZ

in

growth

csZZ-typaa other

0~

hig?eaffindQ

tmnsmoduZatiti

68/,

3.6.

of pxnM+as.

plwrhZ

us

aboZish of

/raf.

ma

context

to know

as

upon

/cmes-taZk/,

the distribution

SO,

&de

RTKa

quiZibrium

at another

thu

Roberts

and

cart&n

a &LW

tlumsmoduZat&m

signaZZing

reaenttu

EGP and n-2/

Zenst

inhamoger,siw

u~topZusn&

faators

It wutd

that

uuuaa

the who&a

rath6r

of suoh

Reaep$or

statea.

As

prusant.

domain8

shift a &nam&

ftuatuattona over

Zn

ratotion

binding mq

ufat

the rectzptor itrraZf.

dzfferunt

RTK

h

betmatm band III nw-

and of diffmt

~nteructions

is ProbnbZu

/Ziks

than

kinaatts, lvlther than

dtitibution

in the dd

rpvitsod

0d8ta

mmzifustation

of 0110receptor

iilutationa in

cuss

the

oonfonnztionaZ

changes

Zargs

measuremmta

sqdZibrZwn

aqtliZibrium

j%ncMon

th&poerribiZiQf.

simpZur

tha moZazuW

Th6s

in the nature

kXnaad

of

much

Z+and

Z*anc-xceptor

dimuric

probabZg

the abitiw

of

decay

moZecuZar

a putative

the subutassoe.

uxpoatud

sxuhangabiZi*

statis,

aasa,

bs

simi-

on or off.

favoured Cs

th6

epruadsng

such

sl/matic flmution

bZnding

weru

Thus,

affuct

==T~J%

a &aamia

that

581. SimiZurZg

forue

aan

anJ~otro~

inaatitra and acttva

this

The

the con+cuous

wittin

activation

has a aompoezztion

aggrqation

/ruf.

eZumenti

ita

Santa subaZaes aZeosupport8

phasphorescenco

c~teghostm~,

RTKS

aocanparr+ag

St8 moctuZat2on8.

apociea ofthe

be-on

probhna

eopactiZZy

crRmbD?l to moat

chang6za

and

tlttzae

RTKe,

of

stzuaturs

aonfo37x&onut

Zigand

as

savts

appZtid

in o&r

A purtCau;larZ~

of

spuuXj%c

this

fat-

and ffZ3a.t

SzgruzZ n&ezcuZe change8

evoked

bu

Zfgund

from

that

binding

to it8

of anothsr

rau8ptor

catt-tgpo,

LiganciGndpndme &ibution not-#pa_

In

Chmzges

Z8ad

witi18

cam

Oth%r8

"phamc.qq+g tive

ceZZ

cun

inactivu

statue

und oncogenic

2

3 4 s. 6. 7, 8. Q 10 II_ 22 73 24 15 16 17 18

in a

the

to

tipnil

ths

b%

on purpoas,

c@amic

of rotationaZ bstwaan

an approaah

prot8in8

and

888m8

or different

of

Sir.08 RTX

phe-

and

stmtotLuvlZ

tigcmd

manner

/CsF--I/

fxwf.

63/

i?h8 uonatStutivoZu factor

Undsrstanding

ha,

Zewst

coutd

OV8vr888ion of

eon-

tmmsfomtzd

ths

indeptit

ths protein

significant

mutations

pathogenatiu

64/.

at

as

pmtuins

in

bl/ ac-

v-$%8

ruueptor

or

uon-

2w az.xzr&d k l&z22 as

bstw88n

d8r%-

active

und

c=SF8ct OfmaZjImution,

aspsots

diffarsnt

ths

ohcmga",

major

/ref.

undmodutatad

be2 a

to

praaanos

oonfonnatfonat

can b8 an important

ahang

dtitanca8

in

oartain

bt~ puti'loganiu thtz dtitr;Lbution

/reef_ 34f. Such

7

aett

8acm8

uhumctaria%ng

%_g.,

od/

id8ntitiZ

io

rtZ8pOTl8&Z,

rzwptors

gene,

txwn8fonnation8

Confoxwutionat, through

c-fh8

8eem8

to infZutznu8 th8m

cetZ-~8

~ttZQOVZiStiC

osrtain

the

is cEBtetin8d

on6

of aZtemtion8

tmmsformztion

transfomn

gutation

of

ths

autivi~

v-8rb-reZutud

m6an8

to

of

OP

a Zigand-inducad

k&a88

fommtion

of

to tha rqxwtuira

on

of

rau%ptor

ZatalvlZ mobiZi:ioa rautiptirs

to antzZ~j8a RTK

or

/rsf_

spitopea

j%nutXun

to us a vial% prom&

pan&-i-cm

with

of

cyan

44/ the

be

aesqjad

or nwasureuwnt same

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