期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 415, 期 1, 页码 221-235出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2011.10.045
关键词
domain swapping; protein evolution; circular permutation; multidomain proteins; fold age
资金
- Hungarian Scientific Research Fund [PD73096, NK77978]
- Hungarian National Office for Research and Technology [NKFP_07_01_-MASPOK07]
- National Science Foundation [DBI 1027394]
- National Institute of General Medical Sciences [GM083107, GM084222]
- Direct For Biological Sciences [1027394] Funding Source: National Science Foundation
- Div Of Biological Infrastructure [1027394] Funding Source: National Science Foundation
Multidomain proteins form in evolution through the concatenation of domains, but structural domains may comprise multiple segments of the chain. In this work, we demonstrate that new multidomain architectures can evolve by an apparent three-dimensional swap of segments between structurally similar domains within a single-chain monomer. By a comprehensive structural search of the current Protein Data Bank (PDB), we identified 32 well-defined segment-swapped proteins (SSPs) belonging to 18 structural families. Nearly 13% of all multidomain proteins in the PDB may have a segment-swapped evolutionary precursor as estimated by more permissive searching criteria. The formation of SSPs can be explained by two principal evolutionary mechanisms: (i) domain swapping and fusion (DSF) and (ii) circular permutation (CP). By large-scale comparative analyses using structural alignment and hidden Markov model methods, it was found that the majority of SSPs have evolved via the DSF mechanism, and a much smaller fraction, via CP. Functional analyses further revealed that segment swapping, which results in two linkers connecting the domains, may impart directed flexibility to multidomain proteins and contributes to the development of new functions. Thus, inter-domain segment swapping represents a novel general mechanism by which new protein folds and multidomain architectures arise in evolution, and SSPs have structural and functional properties that make them worth defining as a separate group. (C) 2011 Elsevier Ltd. All rights reserved.
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