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The nature of sequence and structure divergence in the Haloalkanoate Dehalogenase SuperFamily (HADSF)
Author(s) -
Pandya Chetanya,
Brown Shoshana D,
DunawayMariano Debra,
Babbitt Patricia C,
Xia Yu,
Allen Karen N
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.797.2
Subject(s) - domain (mathematical analysis) , structural similarity , similarity (geometry) , sequence (biology) , protein domain , computational biology , context (archaeology) , structural alignment , protein structure , divergence (linguistics) , sequence alignment , evolutionary biology , computer science , biology , mathematics , peptide sequence , genetics , artificial intelligence , paleontology , linguistics , philosophy , gene , mathematical analysis , biochemistry , image (mathematics)
Though the number of protein folds is predicted to be finite, the universe of protein structures is vast and diverse. Thus understanding evolution of protein folds is a fundamental research challenge. The HADSF serves as an ideal model as it has a modular architecture where the conserved, Rossmann fold core domain is accessorized by a variable cap domain. This work aims to determine the impact of the cap domain on the sequence and structure divergence of the core domain. By performing quantitative analysis on a dataset of core‐domain‐only and cap‐domain‐ only structures, we have uncovered some basic protein design principles. We find that the relationship between sequence and structure divergence is robust, non‐linear (ρ=0.69) and, independent of the corresponding cap type. Core domains with the same cap type share greater similarity (; = 0.76) at the sequence and structure level than core domains with different cap types (; = 0.64), consistent with coevolution of the cap and core domains. Moreover, this similarity between cores is a global phenomenon with contributions from all residues of the Rossmann fold. Together, these results are consistent with coevolution of the cap domain in the context of a thermodynamically stable core domain, a strategy that may be active in other multi‐domain families. This project was supported by National Institute of General Medical Sciences (U54GM093342).