Systematic Detection of Internal Symmetry in Proteins Using CE-Symm

JOURNAL OF MOLECULAR BIOLOGY

卷:426

Article

Myers-Turnbull, Douglas¹  Bliven, Spencer E.²  Rose, Peter W.³  Aziz, Zaid K.⁴  Youkharibache, Philippe⁵  Bourne, Philip E.⁶  Prlic, Andreas³ 

[1] Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Bioinformat & Syst Biol Program, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, San Diego Supercomp Ctr, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[5] InPharmatics Corp, San Diego, CA 92117 USA

[6] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA

关键词: structural biology;    protein evolution;    pseudo-symmetry;    protein function;    symmetry detection;   

DOI  :  10.1016/j.jmb.2014.03.010

来源: Elsevier

【 摘 要 】

Symmetry is an important feature of protein tertiary and quaternary structures that has been associated with protein folding, function, evolution, and stability. Its emergence and ensuing prevalence has been attributed to gene duplications, fusion events, and subsequent evolutionary drift in sequence. This process maintains structural similarity and is further supported by this study. To further investigate the question of how internal symmetry evolved, how symmetry and function are related, and the overall frequency of internal symmetry, we developed an algorithm, CE-Synnm, to detect pseudo-symmetry within the tertiary structure of protein chains. Using a large manually curated benchmark of 1007 protein domains, we show that CE-Symm performs significantly better than previous approaches. We use CE-Synnm to build a census of symmetry among domain superfamilies in SCOP and note that 18% of all superfamilies are pseudo-symmetric. Our results indicate that more domains are pseudo-symmetric than previously estimated. We establish a number of recurring types of symmetry function relationships and describe several characteristic cases in detail. With the use of the Enzyme Commission classification, symmetry was found to be enriched in some enzyme classes but depleted in others. CE-Synnm thus provides a methodology for a more complete and detailed study of the role of symmetry in tertiary protein structure [availability: CE-Symm can be run from the We at http://source.rcsb.org/jfatcatserver/symmetry.jsp. Source code and software binaries are also available under the GNU Lesser General Public License (version 2.1) at https://github.com/rcsb/symmetry. An interactive census of domains identified as symmetric by CE-Synnm is available from http://source.rcsb.org/jfatcatserver/ scopResults.jsp]. (C)2014 The Authors. Published by Elsevier Ltd. on behalf of University of California, San Diego. This is an open access article under the CC BY license

【 授权许可】

Free