Systematic Detection of Internal Symmetry in Proteins Using CE-Symm

Douglas Myers-Turnbull,Spencer E Bliven,Peter W Rose,Zaid K Aziz,Philippe Youkharibache,Philip E Bourne,Andreas Prlić

doi:10.1016/j.jmb.2014.03.010

Douglas Myers-Turnbull, Spencer E Bliven + Show 5 more

Open Access

https://doi.org/10.1016/j.jmb.2014.03.010

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Abstract

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-Symm, 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-Symm 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-Symm 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 Web 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-Symm is available from http://source.rcsb.org/jfatcatserver/scopResults.jsp].

Highlights

Many proteins have a high degree of symmetry in both their tertiary and quaternary structures
The presence and type of symmetry for each of these domains was determined manually, resulting in a table of SCOP IDs with their corresponding space groups presented in Supplemental Table S1
In this study we introduced a new method for determining pseudo-symmetry in protein structure and used it to build a census of symmetry over domains in SCOP

Summary

Introduction

Many proteins have a high degree of symmetry in both their tertiary and quaternary structures. In the case of quaternary symmetry, these substructures are defined by the inherent equivalence of interactions between identical chains, and often can be determined from the space group of the crystal for X-ray structures. This equivalence can be relaxed to allow for evolutionary divergence, revealing pseudo-symmetric arrangements within individual polypeptide chains (internal symmetry) or that span two or more non-identical chains.

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