Structural classification of small, disulfide-rich protein domains

被引:79
作者
Cheek, Sara
Krishna, S. Sri
Grishin, Nick V.
机构
[1] Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA
[2] Univ Calif San Diego, Joint Ctr Struct Genom, La Jolla, CA 92093 USA
[3] Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA
基金
美国国家卫生研究院;
关键词
protein classification; disulfides; small proteins; homology; fold;
D O I
10.1016/j.jmb.2006.03.017
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
Disulfide-rich domains are small protein domains whose global folds are stabilized primarily by the formation of disulfide bonds and, to a much lesser extent, by secondary structure and hydrophobic interactions. Disulfide-rich domains perform a wide variety of roles functioning as growth factors, toxins, enzyme inhibitors, hormones, pheromones, allergens, etc. These domains are commonly found both as independent (single-domain) proteins and as domains within larger polypeptides. Here, we present a comprehensive structural classification of approximately 3000 small, disulfide-rich protein domains. We find that these domains can be arranged into 41 fold groups on the basis of structural similarity. Our fold groups, which describe broader structural relationships than existing groupings of these domains, bring together representatives with previously unacknowledged similarities; 18 of the 41 fold groups include domains from several SCOP folds. Within the fold groups, the domains are assembled into families of homologs. We define 98 families of disulfide-rich domains, some of which include newly detected homologs, particularly among knottin-like domains. On the basis of this classification, we have examined cases of convergent and divergent evolution of functions performed by disulfide-rich proteins. Disulfide bonding patterns in these domains are also evaluated. Reducible disulfide bonding patterns are much less frequent, while symmetric disulfide bonding patterns are more common than expected from random considerations. Examples of variations in disulfide bonding patterns found within families and fold groups are discussed. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:215 / 237
页数:23
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