- Email: [email protected]
Communication among the proteoglycans
TIBS 17 - MAY 1992 22 Mathews, C. K. and van Holde, K. E. (1990) Biochemistry, Benjamin Cummings 23 Meister, A. (1965)in Biochemistry of the Amino Acids p. 748, Academic Press 24 Metzler, D. E. (1977) in Biochemistry p. 834, Academic Press 25 Newsholme, E. A. and Leech, A. R. (1983) in Biochemistry for the Medical Sciences p. 408,
John Wiley 26 Rawn, J. D. (1983) in Biochemistry p. 845, Harper and Row 27 Rawn, J. D. (1989) in Biochemistry p. 477, Harper and Row 28 Rodwell, V. W. (1969) in Metabolic Pathways (Greenberg, D, ed.), p. 198, Academic Press 29 Smith, E. L. et al. (1983) in Principles of
Biochemistry: General Aspects (7th edn) p. 659, McGraw Hill 30 Stryer, L. (1988) in Biochemistry (3rd edn) p. 506, W. H. Freeman 31 Voet, D. and Voet, J. G. (1990) in Biochemistry p. 693, John Wiley 32 White, A. (1973) in Biochemistry p. 688, McGraw Hill
LETTERS A bipartite nuclear targeting motif in protein kinase C? In the December issue of TIBS, Dingwall and Laskey reviewed the wide diversity of nuclear targeting sequences that exists 1. They have identified a bipartite motif in many proteins transported into the nucleus and propose that this motif may serve as a consensus for nuclear targeting. This bipartite motif consists of a downstream cluster of two basic amino acids and an upstream cluster in which three out of five amino acids are basic. Protein kinase C (PKC) sequences from cow, human and rat 2 and rabbit 3 have been examined and this bipartite motif found. Figure 1 compares the motif found in the first and second zinc fingers of PKC isoenzymes from a range of species. There is a distinctive feature in the species examined: in the ct-PKC sequences, glutamine is substituted for arginine in the first basic cluster of the second zinc finger domain. Since ct-PKC has not been localized to the nucleus, this suggests that the replacement of KR by KQ may prevent the targeting of a-PKC to
Communication among the proteoglycans Tim Hunt, in his editorial 'naming names' [TIBS (1992) 17, 1] commented, wryly I suspect, 'You can name your new protein anything you like'. You should be so lucky! In the proteoglycan field you can name any old proteoglycan anything you like, given the amino acid sequence or cDNA for the protein part. In the past two years the nomenclature has taken a bizarre turn, which bodes ill for logical nomenclature development and communication in this field. Names
176
Sequenceconnectedwith the first zincfinger:
bovPKCa bovPKC[~ bovPKC'/ humPKCa humPKCI3 humPKC~/ ratPKCa ratPKC# ratPKCy rabbitPKCa rabbitPKC~ rabbitPKC?
KR KR RR KR RR RR KR KR RR KR KR RR
X21 X21 X21 X21 X21 X21 X21 X21 X21 X21 X21 X21
RxKxKxK RxKxKxK RxKxKxR RxKxKxK RxKxKxK RxKxKxR RxKxKxK RxKxKxK RxKxKxR RxKxKxK RxKxKxK RxKxKxR
Sequenceconnectedwith the secondzincfinger:
bovPKCa bovPKC~ bovPKC~ humPKCa humPKC[5 humPKC~/ ratPKCa ratPKCr~ rat PKC,/ rabbitPKCa
KQ KR RR KQ KR RR KQ RR RR KQ
X15 X15 X15 X15 X15 X15 X15 X15 X15 X15
KRxR RRxR RRxR KRxR RRxR RR~ KRxR RRxR RRxR KRxR
targeting motif. Future research should reveal whether PKC, upon activation, binds to any nuclear protein and whether such binding involves the bipartite motif identified here. References 1 Dingwall, C. and Laskey, R. A. (1991) Trends Biochem. Sci. 16, 478-481 2 Rosenthal, A. et al. (1987) EMBO J. 6, 433-441 30hno, S. et al. (1988) Biochemistry 27, 2083-2087 4 Huang, F. L. et al. (1988) J. Neurosci. 8, 4734-4744 5 Masmoudi, A. et al. (1989) J. Biol. Chem. 264, 1172-1179 6 Rogue, P. et al. (1990) J. Biol. Chem. 265, 4161-4165 7 Hovecar, B. A. and Fields, A. P. (1991) J. Biol. Chem. 266, 28-33
A. N. MALVIYA Centre de Neurochimie CNRS, 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France.
the nucleus. This should be easy to test experimentally. By contrast, both ~PKC 4 and ~PKC 5,6 have been shown to be present in the nucleus and ligand-induced ~-PKC translocation of ~PKC has also been reported 7. Both of these isoenzymes contain the proposed bipartite nuclear
such as decorin, lumican, aggrecan, syndecan, etc. have been applied to molecules that were well recognized in other contexts and in some cases their chemistry was known in detail. These names are short of all chemical information and have no internal consistency. The older terminology was unsatisfactory and sometimes arbitrary, but it did express important chemical facts. Thus, 'small dermatan sulphate proteoglycan' (e.g. DSPG I1) may be a mouthful, and not always the first preference for every worker in the field, but decorin is not an adequate substitute. Similarly, biglycan is a decorin-like molecule with two dermatan sulphate
CHRISTOPH BLOCK Institut fGr Zellbiologie, Biochemie und Biotechnolagie, Universit~t Bremen, Leobner Strasse, 2800 Bremen 33, FRG.
chains, but decorin is not monoglycan. Perhaps this is fortunate, since glycan is already in overwhelming use as a chemical term for any polysaccharide. The argument that the gene product should be recognized by a name seems reasonable, until one considers that aggrecan is less than 10% protein and more than 90% post-translational. The plethora of new names for already wellknown materials adds to the labour and uncertainty of database searches. Through TIBS, we would like to appeal for caution in elaborating names that carry little and perhaps faulty chemical information. We need a consistent nomenclature which recognizes that sometimes well over 50% of the molecule
TIBS 17 - M A Y 1 9 9 2
is not protein. In the meantime, we plead that new names should be used only to qualify the known chemistry, e.g. 'dermatan sulphate proteoglycan (decorin)'. If we allow the anarchy that reigns in protein terminology to spread into fields where post-translational changes effectively square the number of possibilities for heterogeneity, it will lead
to rapid breakdown of communication between colleagues, new arrivals in the field, and all other interested parties.
Fresco-Alberts-Doty model
I have recently introduced the term 'Fresco-Alberts-Doty model', when discussing the general properties of RNA secondary structure in a textbook on the chemistry of nucleic acids 9 and, better late than never, I urge others to adopt this term too.
Two years ago I published a Reflections article in TIBS entitled 'Creation of a general model of RNA spatial organization '] . In this retrospective article, I pointed out that the hairpin loop model of RNA secondary structure, which is more than 30 years old and is used by virtually everyone studying the wonderful world of RNA, was first described by J. Fresco, B. Alberts and P. Doty in an article in Nature 2. These authors clearly predicted all the characteristic elements that make up the secondary structure of each single-stranded RNA. Unfortunately, this crucial discovery is often overlooked by molecular biology textbooks and reviews of RNA structure. I have received many letters in response to my article. Others studying RNA structure during the late 1950s and early 1960s have also contributed a wealth of information (see, for example, Ref. 3), which I am intending to use in a more extensive review. Several people have stressed the major part that Fresco played in solving the macromolecular structure of RNA. Fresco was head of an RNA group in the Doty laboratory at Harvard during the period 1956--1960. He started his research with a detailed analysis of physicochemical properties of RNA analogs - synthetic polynucleotides such as poly(U) and poly(A) complexes (summarized in Refs 4,5). In comparing the results obtained with those from the melting of natural RNA6, Fresco concluded that the secondary RNA structure 'originates from short hairpin loops within the single chain, stabilized by hydrogen bonds made possible by particular sequences of sterically appropriate purines and pyrimidines '7. After a series of experiments with helix-loop structures 8, the general model of RNA secondary structure was published in Nature z. Fresco continued his studies on RNA spatial structure at Princeton University, publishing a series of excellent works on the macromolecular structure of tRNA (see Ref. 7 for review).
H. GREILING Departmentof ClinicalBiochemistry,RWTH, Aachen, Germany.
J. E. SCOTT
A. LINKER
Chemistry Building,Universityof Manchester, Manchester, UK M13 9PL.
VA MedicalCenter, Hills RoadBlvd, Salt LakeCity, UT84148, USA.
References 1 Bogdanov,A. A. (1989) Trends Biochem. Sci. 14, 505-507 2 Fresco,J. R., Alberts, B. M. and Doty, P. (1960) Nature 188, 98-101 3 Littauer,U. Z. and Eisenberg,H. (1990) Trends Biochem. Sci. 15, 218 4 Doty, P. et al. (1959) Ann. N. Y. Acad. Sci. 81, 693-708 5 Fresco,J. R. (1963) in Informational
Macromolecules (Vogel,H. J., Bryson,V. and
Lampen,J. 0., eds), pp. 121-142, Academic Press 6 Doty, P. et al. (1959) Proc. Natl Acad. Sci. USA 45, 482-489 7 Fresco,J. R. (1959) Trans. N. Y. Acad. Sci. 21, 653-658 8 Fresco,J. R. et al. (1966) Cold Spring Harbor Syrup. Quant. Biol. 31, 527-537 9 Shabarova,Z. A. and Bogdanov,A. A. Chemistry of Nucleic Acids, VHF(in press)
ALEXEY A. BOGDANOV A. N. BelozerskyInstitute of Physicochemical Biology,MoscowState University,Moscow119899, Russia.
Nomenclaturematters: carboxylmethylation Few people are fascinated by nomenclature but most recognize its importance in conveying ideas accurately and clearly. At TIBS we are especially concerned with the correct use of terms, since the journal is widely used by teachers and their students. However, mistakes do sometimes slip through. Dr W. R. Paukovits of the University of Vienna has pointed out a nomenclature error in a recent TIBS article [Spiegel, A. M. et aL (1991) Trends Biochem. Sci. 16, 338-341]. In this article on membrane association of G proteins, the term carboxymethylation was used to describe the formation of a methyl ester by attachment of a methyl group to a carboxyl group: R-COOH ~ R-CO-CH3 This esterification should have been described as a carboxyl methylation (two separate words). As Dr Paukovits has rightly pointed out, carboxymethylation describes the attachment of a CH2-COOHgroup to the -SH group of thiols: R-SH ~ R-S-CH2-COOH The nomenclature committees of the IUBMB and lUPAC have recognized that, particularly in speech, carboxymethylation and carboxyl methylation are easily confused. Thus they have recommended the use of the expanded term carboxyl O-methylation to describe the methyl esterification. TIBS will adopt this term and we hope our readers will do the same.
Competition: Never a dull enzyme? 'I have never known a dull enzyme' (ArthurKomberg) We invite readers to challenge Kornberg's axiom by submitting examples of truly boring enzymes, justifying their nomination in not more than 150 words. Poems or drawings are, naturally, acceptable. Winning entries will be published in TIBS and their authors will receive a one-year free subscription to the journal.
177
John Wiley 26 Rawn, J. D. (1983) in Biochemistry p. 845, Harper and Row 27 Rawn, J. D. (1989) in Biochemistry p. 477, Harper and Row 28 Rodwell, V. W. (1969) in Metabolic Pathways (Greenberg, D, ed.), p. 198, Academic Press 29 Smith, E. L. et al. (1983) in Principles of
Biochemistry: General Aspects (7th edn) p. 659, McGraw Hill 30 Stryer, L. (1988) in Biochemistry (3rd edn) p. 506, W. H. Freeman 31 Voet, D. and Voet, J. G. (1990) in Biochemistry p. 693, John Wiley 32 White, A. (1973) in Biochemistry p. 688, McGraw Hill
LETTERS A bipartite nuclear targeting motif in protein kinase C? In the December issue of TIBS, Dingwall and Laskey reviewed the wide diversity of nuclear targeting sequences that exists 1. They have identified a bipartite motif in many proteins transported into the nucleus and propose that this motif may serve as a consensus for nuclear targeting. This bipartite motif consists of a downstream cluster of two basic amino acids and an upstream cluster in which three out of five amino acids are basic. Protein kinase C (PKC) sequences from cow, human and rat 2 and rabbit 3 have been examined and this bipartite motif found. Figure 1 compares the motif found in the first and second zinc fingers of PKC isoenzymes from a range of species. There is a distinctive feature in the species examined: in the ct-PKC sequences, glutamine is substituted for arginine in the first basic cluster of the second zinc finger domain. Since ct-PKC has not been localized to the nucleus, this suggests that the replacement of KR by KQ may prevent the targeting of a-PKC to
Communication among the proteoglycans Tim Hunt, in his editorial 'naming names' [TIBS (1992) 17, 1] commented, wryly I suspect, 'You can name your new protein anything you like'. You should be so lucky! In the proteoglycan field you can name any old proteoglycan anything you like, given the amino acid sequence or cDNA for the protein part. In the past two years the nomenclature has taken a bizarre turn, which bodes ill for logical nomenclature development and communication in this field. Names
176
Sequenceconnectedwith the first zincfinger:
bovPKCa bovPKC[~ bovPKC'/ humPKCa humPKCI3 humPKC~/ ratPKCa ratPKC# ratPKCy rabbitPKCa rabbitPKC~ rabbitPKC?
KR KR RR KR RR RR KR KR RR KR KR RR
X21 X21 X21 X21 X21 X21 X21 X21 X21 X21 X21 X21
RxKxKxK RxKxKxK RxKxKxR RxKxKxK RxKxKxK RxKxKxR RxKxKxK RxKxKxK RxKxKxR RxKxKxK RxKxKxK RxKxKxR
Sequenceconnectedwith the secondzincfinger:
bovPKCa bovPKC~ bovPKC~ humPKCa humPKC[5 humPKC~/ ratPKCa ratPKCr~ rat PKC,/ rabbitPKCa
KQ KR RR KQ KR RR KQ RR RR KQ
X15 X15 X15 X15 X15 X15 X15 X15 X15 X15
KRxR RRxR RRxR KRxR RRxR RR~ KRxR RRxR RRxR KRxR
targeting motif. Future research should reveal whether PKC, upon activation, binds to any nuclear protein and whether such binding involves the bipartite motif identified here. References 1 Dingwall, C. and Laskey, R. A. (1991) Trends Biochem. Sci. 16, 478-481 2 Rosenthal, A. et al. (1987) EMBO J. 6, 433-441 30hno, S. et al. (1988) Biochemistry 27, 2083-2087 4 Huang, F. L. et al. (1988) J. Neurosci. 8, 4734-4744 5 Masmoudi, A. et al. (1989) J. Biol. Chem. 264, 1172-1179 6 Rogue, P. et al. (1990) J. Biol. Chem. 265, 4161-4165 7 Hovecar, B. A. and Fields, A. P. (1991) J. Biol. Chem. 266, 28-33
A. N. MALVIYA Centre de Neurochimie CNRS, 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France.
the nucleus. This should be easy to test experimentally. By contrast, both ~PKC 4 and ~PKC 5,6 have been shown to be present in the nucleus and ligand-induced ~-PKC translocation of ~PKC has also been reported 7. Both of these isoenzymes contain the proposed bipartite nuclear
such as decorin, lumican, aggrecan, syndecan, etc. have been applied to molecules that were well recognized in other contexts and in some cases their chemistry was known in detail. These names are short of all chemical information and have no internal consistency. The older terminology was unsatisfactory and sometimes arbitrary, but it did express important chemical facts. Thus, 'small dermatan sulphate proteoglycan' (e.g. DSPG I1) may be a mouthful, and not always the first preference for every worker in the field, but decorin is not an adequate substitute. Similarly, biglycan is a decorin-like molecule with two dermatan sulphate
CHRISTOPH BLOCK Institut fGr Zellbiologie, Biochemie und Biotechnolagie, Universit~t Bremen, Leobner Strasse, 2800 Bremen 33, FRG.
chains, but decorin is not monoglycan. Perhaps this is fortunate, since glycan is already in overwhelming use as a chemical term for any polysaccharide. The argument that the gene product should be recognized by a name seems reasonable, until one considers that aggrecan is less than 10% protein and more than 90% post-translational. The plethora of new names for already wellknown materials adds to the labour and uncertainty of database searches. Through TIBS, we would like to appeal for caution in elaborating names that carry little and perhaps faulty chemical information. We need a consistent nomenclature which recognizes that sometimes well over 50% of the molecule
TIBS 17 - M A Y 1 9 9 2
is not protein. In the meantime, we plead that new names should be used only to qualify the known chemistry, e.g. 'dermatan sulphate proteoglycan (decorin)'. If we allow the anarchy that reigns in protein terminology to spread into fields where post-translational changes effectively square the number of possibilities for heterogeneity, it will lead
to rapid breakdown of communication between colleagues, new arrivals in the field, and all other interested parties.
Fresco-Alberts-Doty model
I have recently introduced the term 'Fresco-Alberts-Doty model', when discussing the general properties of RNA secondary structure in a textbook on the chemistry of nucleic acids 9 and, better late than never, I urge others to adopt this term too.
Two years ago I published a Reflections article in TIBS entitled 'Creation of a general model of RNA spatial organization '] . In this retrospective article, I pointed out that the hairpin loop model of RNA secondary structure, which is more than 30 years old and is used by virtually everyone studying the wonderful world of RNA, was first described by J. Fresco, B. Alberts and P. Doty in an article in Nature 2. These authors clearly predicted all the characteristic elements that make up the secondary structure of each single-stranded RNA. Unfortunately, this crucial discovery is often overlooked by molecular biology textbooks and reviews of RNA structure. I have received many letters in response to my article. Others studying RNA structure during the late 1950s and early 1960s have also contributed a wealth of information (see, for example, Ref. 3), which I am intending to use in a more extensive review. Several people have stressed the major part that Fresco played in solving the macromolecular structure of RNA. Fresco was head of an RNA group in the Doty laboratory at Harvard during the period 1956--1960. He started his research with a detailed analysis of physicochemical properties of RNA analogs - synthetic polynucleotides such as poly(U) and poly(A) complexes (summarized in Refs 4,5). In comparing the results obtained with those from the melting of natural RNA6, Fresco concluded that the secondary RNA structure 'originates from short hairpin loops within the single chain, stabilized by hydrogen bonds made possible by particular sequences of sterically appropriate purines and pyrimidines '7. After a series of experiments with helix-loop structures 8, the general model of RNA secondary structure was published in Nature z. Fresco continued his studies on RNA spatial structure at Princeton University, publishing a series of excellent works on the macromolecular structure of tRNA (see Ref. 7 for review).
H. GREILING Departmentof ClinicalBiochemistry,RWTH, Aachen, Germany.
J. E. SCOTT
A. LINKER
Chemistry Building,Universityof Manchester, Manchester, UK M13 9PL.
VA MedicalCenter, Hills RoadBlvd, Salt LakeCity, UT84148, USA.
References 1 Bogdanov,A. A. (1989) Trends Biochem. Sci. 14, 505-507 2 Fresco,J. R., Alberts, B. M. and Doty, P. (1960) Nature 188, 98-101 3 Littauer,U. Z. and Eisenberg,H. (1990) Trends Biochem. Sci. 15, 218 4 Doty, P. et al. (1959) Ann. N. Y. Acad. Sci. 81, 693-708 5 Fresco,J. R. (1963) in Informational
Macromolecules (Vogel,H. J., Bryson,V. and
Lampen,J. 0., eds), pp. 121-142, Academic Press 6 Doty, P. et al. (1959) Proc. Natl Acad. Sci. USA 45, 482-489 7 Fresco,J. R. (1959) Trans. N. Y. Acad. Sci. 21, 653-658 8 Fresco,J. R. et al. (1966) Cold Spring Harbor Syrup. Quant. Biol. 31, 527-537 9 Shabarova,Z. A. and Bogdanov,A. A. Chemistry of Nucleic Acids, VHF(in press)
ALEXEY A. BOGDANOV A. N. BelozerskyInstitute of Physicochemical Biology,MoscowState University,Moscow119899, Russia.
Nomenclaturematters: carboxylmethylation Few people are fascinated by nomenclature but most recognize its importance in conveying ideas accurately and clearly. At TIBS we are especially concerned with the correct use of terms, since the journal is widely used by teachers and their students. However, mistakes do sometimes slip through. Dr W. R. Paukovits of the University of Vienna has pointed out a nomenclature error in a recent TIBS article [Spiegel, A. M. et aL (1991) Trends Biochem. Sci. 16, 338-341]. In this article on membrane association of G proteins, the term carboxymethylation was used to describe the formation of a methyl ester by attachment of a methyl group to a carboxyl group: R-COOH ~ R-CO-CH3 This esterification should have been described as a carboxyl methylation (two separate words). As Dr Paukovits has rightly pointed out, carboxymethylation describes the attachment of a CH2-COOHgroup to the -SH group of thiols: R-SH ~ R-S-CH2-COOH The nomenclature committees of the IUBMB and lUPAC have recognized that, particularly in speech, carboxymethylation and carboxyl methylation are easily confused. Thus they have recommended the use of the expanded term carboxyl O-methylation to describe the methyl esterification. TIBS will adopt this term and we hope our readers will do the same.
Competition: Never a dull enzyme? 'I have never known a dull enzyme' (ArthurKomberg) We invite readers to challenge Kornberg's axiom by submitting examples of truly boring enzymes, justifying their nomination in not more than 150 words. Poems or drawings are, naturally, acceptable. Winning entries will be published in TIBS and their authors will receive a one-year free subscription to the journal.
177