TOPOLOGICAL SIMILARITIES IN TGF-BETA-2, PDGF-BB AND NGF DEFINE A SUPERFAMILY OF POLYPEPTIDE GROWTH-FACTORS

被引:111
作者
MURRAYRUST, J
MCDONALD, NQ
BLUNDELL, TL
HOSANG, M
OEFNER, C
WINKLER, F
BRADSHAW, RA
机构
[1] COLUMBIA UNIV,COLL PHYSICIANS & SURGEONS,NEW YORK,NY 10032
[2] F HOFFMAN LA ROCHE LTD,DEPT PHARMACEUT RES,CH-4002 BASEL,SWITZERLAND
[3] UNIV CALIF IRVINE,COLL MED,DEPT BIOL CHEM,IRVINE,CA 92717
关键词
DISULFIDE KNOT; GROWTH FACTOR; X-RAY STRUCTURE;
D O I
10.1016/0969-2126(93)90029-G
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: The development of functional diversity through gene duplication and subsequent divergent evolution can give rise to proteins that have little or no sequence similarity, but retain similar topologies. Results: The crystal structures of nerve growth factor, transforming growth factor-beta 2 and platelet-derived growth factor-BB show that all three are based on a cystine-knot plus beta-strands topology. There is very little sequence identity between the three proteins and the relationship between the structures had not been deduced from sequence comparisons. Each growth factor is usually active as a dimer; each exists as a dimer in the crystal, but the relative orientations of the protomers are different in each case. Conclusion: The structural motif of disulphide bonds and hydrogen-bonded beta-strands unexpectedly found in these three growth factors acts asa stable framework for elaboration of loops of low sequence similarity that contain the specificity for receptor interaction.
引用
收藏
页码:153 / 159
页数:7
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