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Recognition of opsin to the longitudinal length of retinal isomers in the formation of rhodopsin
WI-6989875
05001~0607x)?
00.0
LETTER TO THE EDITORS
RECOGNITrON OF OPSIN TO THE LONGITUDINAL LENGTH OF RETINAL ISOMERS IN THE FORMATION OF RHO~OPS~N (Received 3 Septmber 19773
Recent reports on the ability of cattle opsin to form photosensitive pigments with 9,13-dicis (Crouch, Purvin. Nakanishi and Ebrey, 1975). ‘I-cis, 79-dicis, 7.13-d&, and 7,9.13-r&is (I&&rip, Liu. Ramamurthy and Asato. 1976) retina1 isomers seem to refute the old idea that opsin has a highly restricted selectivity against the shape of retinal isomers on the premise that opsin can combine only with an ll-cis or 9-&s retinal isomer (Hubbard and Wald, 1952). The present report gives a new concept OF the geometric specificity of cattle opsin. fn a previous paper (Matsumoto and Yoshizawa, 1975) we found the competitive inhibition of the regeneration of rhodopsin by @ionone, and suggested the existence of a /3-ionone ring-binding site in the rhodopsin molecule. ll-cis retinal could link with opsin through the hydrophobic bond in the B-ionone ~n~binding site at one end, and at the other end through a protonated Schiff base between the aldehyde group of retinal and the e-amino group of a lysyl residue of opsin (Bownds, 1967). Thus one can expect that in rhodopsin, and also in artificial visual pigments derived From retinal isomers or its analogues, the lengths of retinal isomers or analogues should be Fairly timited. There is fittle information about the tag-~mens~ona1 geometries of il-cis retinal in rhodopsin and also of other retinal isomers or analogues in the artificial visual pigments Accordingly, one cannot estimate accurately the true longitudinal size of every retinal isomer or analogue in a pigment. For simpticity our discussion will be limited only to retinal isomers. Let us define the ion~tudin~l size
(i.e. the length), 1, of all the sixteen isomers of retinal as the distance from* C-15 to the center of the b-ionone ring of retinal. Rshould be noted that the true longitudinal size of each isomer which opsin must dis~minate is not equal to I, but slightly larger than 1. In order to evaluate I of all isomers- the following simp~~catio~s were made: (1) All the retinal isomers are planar molecules; (2) all the C-C-C bond angles are equal to 120’; (3) all the C-C distances of single bonds are equal to a, those of double bonds to b; (4) all the single bonds in the side chain are in truss conjurations (previously the 12s bond OF 1l-c& retinal was supposed by Honig and Karplus, 1971 to be in cis configuration in rhodopsin, but a recent analogue study of 14-methyl retinal by Ebrey, Govindjee, Honig, Pollock, Chan, Crouch, Yudd and Nakanishi, 1975, suggests the rru~s configuration): (5) the &ionone ring has a hexagonal shape made from six single bonds. On the basis of the above-mentioned simplifications al1 the sixteen geometrical isomers of retinal are shown in Fig. 1. As can be seen ali the isomers were classified into four groups according to the magnitudes of 1. The values can be evaluated using the Pythagorean theorem, because a and b are known to a good approximation. The X-ray analyses of nystal II-cis and al&runs retinals (Sperhng 1973) and the all-trans retinylidene Schiff base in a protonated form (Hamanaka, Mitsui and Azuma, 1973) showed that a varies from 1.46 to 1.48 A and b from 1.33 to 1.35 A in Free retinal& and that a varies from 1.44 to f.48 A and b from 1.34 to I.36 A in the protonated
Fig. 1. 607
Schiff base. Assuming that a is 1.46 A and b is 1.35 A, one can estimate I at 12.4A in the P, group (we will call this all-trans group), il.0 A in the P2 (or 13-cis) group, 10.1 A in the P, and Ps groups (or 11-cis and 7-cis groups respectively), and 9.78 A in the P, group (or 9-cis group). Active retinal isomers, which can form photosensitive pigments in combination with opsin, are marked with a sirperscript circle (“), and inactive ones with a cross (‘). Other isomers have never been examined. A11 the active retina1 isomers except 7,9-&is retina1 can be ciassified into two groups-10.1 A (1 l-&s and 7-cis groups) and 9.78 A (9-cis group) in I. Thus the reactive group has the same or a smaller value in 1 compared to that of the 11-cis group. In contrast, inactive isomers have much greater t values: all-truns (12.4 A) and ifcis (11.0 A)retinals. Now we propose that opsin has the ability to discriminate the longitudinal size of a retinal isomer. In our mechanism of the regeneration of rhodopsin, the fast binding of the fl-ionone ring of 11-cis retinal to opsin through a hydrophobic bond forms an 11-cis retinal*opsin complex as the first step, in which no Schiff base linkage yet forms. If the carbonyl carbon (C-15) of retinal in such an 11-cis retinal-opsin complex is close enough to be attacked by the c-amino nitrogen of the lysyi residue in opsin, the Schiff base can be formed as the second step. In such a fashion opsin can select the retinal isomers suitable for the pigment formation in recognition of the longi-
instead of a hexagonal shape. which represents a #J-ionone ring. These low specificities for the side chain and for the orientation of the ,i%ionone ring may have its origin in the hydrophobic nature of binding. Only one exceptional case in the above discussions is 7,9-d& retinal, which belongs to the 13-c& group and has the ability to combine with opsin to form a photosensitive pigment (DeGrip er ai., 1976). Since 7,9-dicis retinal has the highly hindered o1efinic linkage in the ring and the side chain, the torsion in the linkage could result in some shortening of the true longitudinal size of 79-dicis retinal in the pigment. It is noteworthy that the binding rates of ‘I-&s isomers with opsin were 150 times smaller than that of 1I-cis retinal (DeGrip et al., 1976). This may be responsible for the bad proximity of C-15 to the r-amino group of lysine in intermediate complexes composed of opsin and 7-cis retinal isomers caused by such highly hindered 7-cis linkage. Further studies of retinal isomers both on the binding abihty with opsin and on the kinetic parameters of the binding are hoped to clarify the redn&opsin interaction in rhodopsin. Acknowledgements-This work was supported in part by grants from the Japan Society for the Promotion of $eienee to Hiroyuki Matsumoto and from the Japanese Ministry of Education to T&u Yoshizawa
tudinal sizes. in Fig. 2 all the monocis and ah-rrrms isomers of
retinal were overlapped at the center of the &ionone ring so as to display the same longitudinal direction. The fact that the three monocis (i.e. ‘I-cis, 9-cb and 11-cis) and other di-, or tricis retinals can combine with opsin as long as they have the 1ongitnciinaI length, I, of co. 10 A (i.e. they belong to the 7-c& 9-cis or 11-cis group), indicates that opsin has rela-
tively low stereo-specificity in the side chain-binding site. The specificity of the orientation of the fl-ionone ring seems also to be low. One of the most typieai example is the fact that the ‘I-cis isomers (7-c& 7,9-dicis, 7,13_dicis and 7,9,13-tricis) can bind with opsin, in which the okfinic linkages in the ring and the side chain are not on a plane (~amamu~hy, Bopp
and Liu, 1972). as indicated
in the figure by a line
KyotdUkoersity
Kyoto Japan
REFERENCES Bow& D. (1967) Site of attachment of retinal in rhodopsin. Nature 216, 1178-f 181. Crouch R.. Purvin V., Nakanishi K. and Ebrcy T. (1975) Isorhodopsin II: Artitleial photosensitive pigment formed from 9,13-dicir rctinai. Prof. Nom. Acad. Sci. U.S.A. 72 1538-1542. DeGrip W. J., Liu R. S. H., Ramamu~hy V. and Asato A. (1976) Rhodopsin analogues from highly hindered 7-cis isomers of retinal. Narure 262, 416418.
Letter to the Editors Ebrey T.. Govindjee R.. Honig B., Pollocb E., Ghan W.. Crouch R.. Yudd A. and Nakanishi K. (f975) Properties of several stericatly modified retinal analogs and their photosensitive pigments. ~i~e~i~~y 14, 3933-3941. Hamanaka T., Mitsui T. and Atuma K. (1973) The Twelfth Annuaf Meeting Abstracts of the Biophysicat Society of Japan (in Japanese) 81. Honig B. and Karplus M. (1971) Imputations of torsional potential of retinal isomers for visual excitation. Nature 229, 558-560. Hubbard R. and Waid G. (1952) Cis-trans isomers of vita-
609
min A and retinene in the rhodopsin system. J. gen. f!tysioI. 36, 269-315. Matsumoto H. and Yoshizawa T. (1975) Existence of a p-ionone ~ng-bind~3 site in the rhodopsin molecule. Karure 250, 523-526. Ramamurthy V., Bopp T. T. and Liu R. S. H. (1972) NMR studies of 7-cis-8_ionoi and related compounds. Ringchain conformationa preference. ~er~u~edron Len. 37, 3915-3916. Sperling W. (1973) Coronations of I I-&s retinal. In Biochemisnp and F~~siol~y of visnul ~jg~ents (Edited by Langer H.), 19-28. Springer, Berlin.
05001~0607x)?
00.0
LETTER TO THE EDITORS
RECOGNITrON OF OPSIN TO THE LONGITUDINAL LENGTH OF RETINAL ISOMERS IN THE FORMATION OF RHO~OPS~N (Received 3 Septmber 19773
Recent reports on the ability of cattle opsin to form photosensitive pigments with 9,13-dicis (Crouch, Purvin. Nakanishi and Ebrey, 1975). ‘I-cis, 79-dicis, 7.13-d&, and 7,9.13-r&is (I&&rip, Liu. Ramamurthy and Asato. 1976) retina1 isomers seem to refute the old idea that opsin has a highly restricted selectivity against the shape of retinal isomers on the premise that opsin can combine only with an ll-cis or 9-&s retinal isomer (Hubbard and Wald, 1952). The present report gives a new concept OF the geometric specificity of cattle opsin. fn a previous paper (Matsumoto and Yoshizawa, 1975) we found the competitive inhibition of the regeneration of rhodopsin by @ionone, and suggested the existence of a /3-ionone ring-binding site in the rhodopsin molecule. ll-cis retinal could link with opsin through the hydrophobic bond in the B-ionone ~n~binding site at one end, and at the other end through a protonated Schiff base between the aldehyde group of retinal and the e-amino group of a lysyl residue of opsin (Bownds, 1967). Thus one can expect that in rhodopsin, and also in artificial visual pigments derived From retinal isomers or its analogues, the lengths of retinal isomers or analogues should be Fairly timited. There is fittle information about the tag-~mens~ona1 geometries of il-cis retinal in rhodopsin and also of other retinal isomers or analogues in the artificial visual pigments Accordingly, one cannot estimate accurately the true longitudinal size of every retinal isomer or analogue in a pigment. For simpticity our discussion will be limited only to retinal isomers. Let us define the ion~tudin~l size
(i.e. the length), 1, of all the sixteen isomers of retinal as the distance from* C-15 to the center of the b-ionone ring of retinal. Rshould be noted that the true longitudinal size of each isomer which opsin must dis~minate is not equal to I, but slightly larger than 1. In order to evaluate I of all isomers- the following simp~~catio~s were made: (1) All the retinal isomers are planar molecules; (2) all the C-C-C bond angles are equal to 120’; (3) all the C-C distances of single bonds are equal to a, those of double bonds to b; (4) all the single bonds in the side chain are in truss conjurations (previously the 12s bond OF 1l-c& retinal was supposed by Honig and Karplus, 1971 to be in cis configuration in rhodopsin, but a recent analogue study of 14-methyl retinal by Ebrey, Govindjee, Honig, Pollock, Chan, Crouch, Yudd and Nakanishi, 1975, suggests the rru~s configuration): (5) the &ionone ring has a hexagonal shape made from six single bonds. On the basis of the above-mentioned simplifications al1 the sixteen geometrical isomers of retinal are shown in Fig. 1. As can be seen ali the isomers were classified into four groups according to the magnitudes of 1. The values can be evaluated using the Pythagorean theorem, because a and b are known to a good approximation. The X-ray analyses of nystal II-cis and al&runs retinals (Sperhng 1973) and the all-trans retinylidene Schiff base in a protonated form (Hamanaka, Mitsui and Azuma, 1973) showed that a varies from 1.46 to 1.48 A and b from 1.33 to 1.35 A in Free retinal& and that a varies from 1.44 to f.48 A and b from 1.34 to I.36 A in the protonated
Fig. 1. 607
Schiff base. Assuming that a is 1.46 A and b is 1.35 A, one can estimate I at 12.4A in the P, group (we will call this all-trans group), il.0 A in the P2 (or 13-cis) group, 10.1 A in the P, and Ps groups (or 11-cis and 7-cis groups respectively), and 9.78 A in the P, group (or 9-cis group). Active retinal isomers, which can form photosensitive pigments in combination with opsin, are marked with a sirperscript circle (“), and inactive ones with a cross (‘). Other isomers have never been examined. A11 the active retina1 isomers except 7,9-&is retina1 can be ciassified into two groups-10.1 A (1 l-&s and 7-cis groups) and 9.78 A (9-cis group) in I. Thus the reactive group has the same or a smaller value in 1 compared to that of the 11-cis group. In contrast, inactive isomers have much greater t values: all-truns (12.4 A) and ifcis (11.0 A)retinals. Now we propose that opsin has the ability to discriminate the longitudinal size of a retinal isomer. In our mechanism of the regeneration of rhodopsin, the fast binding of the fl-ionone ring of 11-cis retinal to opsin through a hydrophobic bond forms an 11-cis retinal*opsin complex as the first step, in which no Schiff base linkage yet forms. If the carbonyl carbon (C-15) of retinal in such an 11-cis retinal-opsin complex is close enough to be attacked by the c-amino nitrogen of the lysyi residue in opsin, the Schiff base can be formed as the second step. In such a fashion opsin can select the retinal isomers suitable for the pigment formation in recognition of the longi-
instead of a hexagonal shape. which represents a #J-ionone ring. These low specificities for the side chain and for the orientation of the ,i%ionone ring may have its origin in the hydrophobic nature of binding. Only one exceptional case in the above discussions is 7,9-d& retinal, which belongs to the 13-c& group and has the ability to combine with opsin to form a photosensitive pigment (DeGrip er ai., 1976). Since 7,9-dicis retinal has the highly hindered o1efinic linkage in the ring and the side chain, the torsion in the linkage could result in some shortening of the true longitudinal size of 79-dicis retinal in the pigment. It is noteworthy that the binding rates of ‘I-&s isomers with opsin were 150 times smaller than that of 1I-cis retinal (DeGrip et al., 1976). This may be responsible for the bad proximity of C-15 to the r-amino group of lysine in intermediate complexes composed of opsin and 7-cis retinal isomers caused by such highly hindered 7-cis linkage. Further studies of retinal isomers both on the binding abihty with opsin and on the kinetic parameters of the binding are hoped to clarify the redn&opsin interaction in rhodopsin. Acknowledgements-This work was supported in part by grants from the Japan Society for the Promotion of $eienee to Hiroyuki Matsumoto and from the Japanese Ministry of Education to T&u Yoshizawa
tudinal sizes. in Fig. 2 all the monocis and ah-rrrms isomers of
retinal were overlapped at the center of the &ionone ring so as to display the same longitudinal direction. The fact that the three monocis (i.e. ‘I-cis, 9-cb and 11-cis) and other di-, or tricis retinals can combine with opsin as long as they have the 1ongitnciinaI length, I, of co. 10 A (i.e. they belong to the 7-c& 9-cis or 11-cis group), indicates that opsin has rela-
tively low stereo-specificity in the side chain-binding site. The specificity of the orientation of the fl-ionone ring seems also to be low. One of the most typieai example is the fact that the ‘I-cis isomers (7-c& 7,9-dicis, 7,13_dicis and 7,9,13-tricis) can bind with opsin, in which the okfinic linkages in the ring and the side chain are not on a plane (~amamu~hy, Bopp
and Liu, 1972). as indicated
in the figure by a line
KyotdUkoersity
Kyoto Japan
REFERENCES Bow& D. (1967) Site of attachment of retinal in rhodopsin. Nature 216, 1178-f 181. Crouch R.. Purvin V., Nakanishi K. and Ebrcy T. (1975) Isorhodopsin II: Artitleial photosensitive pigment formed from 9,13-dicir rctinai. Prof. Nom. Acad. Sci. U.S.A. 72 1538-1542. DeGrip W. J., Liu R. S. H., Ramamu~hy V. and Asato A. (1976) Rhodopsin analogues from highly hindered 7-cis isomers of retinal. Narure 262, 416418.
Letter to the Editors Ebrey T.. Govindjee R.. Honig B., Pollocb E., Ghan W.. Crouch R.. Yudd A. and Nakanishi K. (f975) Properties of several stericatly modified retinal analogs and their photosensitive pigments. ~i~e~i~~y 14, 3933-3941. Hamanaka T., Mitsui T. and Atuma K. (1973) The Twelfth Annuaf Meeting Abstracts of the Biophysicat Society of Japan (in Japanese) 81. Honig B. and Karplus M. (1971) Imputations of torsional potential of retinal isomers for visual excitation. Nature 229, 558-560. Hubbard R. and Waid G. (1952) Cis-trans isomers of vita-
609
min A and retinene in the rhodopsin system. J. gen. f!tysioI. 36, 269-315. Matsumoto H. and Yoshizawa T. (1975) Existence of a p-ionone ~ng-bind~3 site in the rhodopsin molecule. Karure 250, 523-526. Ramamurthy V., Bopp T. T. and Liu R. S. H. (1972) NMR studies of 7-cis-8_ionoi and related compounds. Ringchain conformationa preference. ~er~u~edron Len. 37, 3915-3916. Sperling W. (1973) Coronations of I I-&s retinal. In Biochemisnp and F~~siol~y of visnul ~jg~ents (Edited by Langer H.), 19-28. Springer, Berlin.