TY - JOUR
T1 - Loss of quaternary structure is associated with rapid sequence divergence in the OSBS family
AU - Odokonyero, Denis
AU - Sakai, Ayano
AU - Patskovsky, Yury
AU - Malashkevich, Vladimir N.
AU - Fedorov, Alexander A.
AU - Bonanno, Jeffrey B.
AU - Fedorov, Elena V.
AU - Toro, Rafael
AU - Agarwal, Rakhi
AU - Wang, Chenxi
AU - Ozerova, Nicole D.S.
AU - Yew, Wen Shan
AU - Sauder, J. Michael
AU - Swaminathan, Subramanyam
AU - Burley, Stephen K.
AU - Almo, Steven C.
AU - Glasner, Margaret E.
PY - 2014/6/10
Y1 - 2014/6/10
N2 - The rate of protein evolution is determined by a combination of selective pressure on protein function and biophysical constraints on protein folding and structure. Determining the relative contributions of these properties is an unsolved problem in molecular evolution with broad implications for protein engineering and function prediction. As a case study, we examined the structural divergence of the rapidly evolving o-succinylbenzoate synthase (OSBS) family, which catalyzes a step in menaquinone synthesis in diverse microorganisms and plants. On average, the OSBS family is much more divergent than other protein families from the same set of species, with the most divergent family members sharing <15% sequence identity. Comparing 11 representative structures revealed that loss of quaternary structure and large deletions or insertions are associated with the family's rapid evolution. Neither of these properties has been investigated in previous studies to identify factors that affect the rate of protein evolution. Intriguingly, one subfamily retained a multimeric quaternary structure and has small insertions and deletions compared with related enzymes that catalyze diverse reactions. Many proteins in this subfamily catalyze both OSBS and N-succinylamino acid racemization (NSAR). Retention of ancestral structural characteristics in the NSAR/OSBS subfamily suggests that the rate of protein evolution is not proportional to the capacity to evolve new protein functions. Instead, structural features that are conserved among proteins with diverse functions might contribute to the evolution of new functions.
AB - The rate of protein evolution is determined by a combination of selective pressure on protein function and biophysical constraints on protein folding and structure. Determining the relative contributions of these properties is an unsolved problem in molecular evolution with broad implications for protein engineering and function prediction. As a case study, we examined the structural divergence of the rapidly evolving o-succinylbenzoate synthase (OSBS) family, which catalyzes a step in menaquinone synthesis in diverse microorganisms and plants. On average, the OSBS family is much more divergent than other protein families from the same set of species, with the most divergent family members sharing <15% sequence identity. Comparing 11 representative structures revealed that loss of quaternary structure and large deletions or insertions are associated with the family's rapid evolution. Neither of these properties has been investigated in previous studies to identify factors that affect the rate of protein evolution. Intriguingly, one subfamily retained a multimeric quaternary structure and has small insertions and deletions compared with related enzymes that catalyze diverse reactions. Many proteins in this subfamily catalyze both OSBS and N-succinylamino acid racemization (NSAR). Retention of ancestral structural characteristics in the NSAR/OSBS subfamily suggests that the rate of protein evolution is not proportional to the capacity to evolve new protein functions. Instead, structural features that are conserved among proteins with diverse functions might contribute to the evolution of new functions.
KW - Enolase superfamily
KW - Protein structure
KW - Protein structure-function relationships
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U2 - 10.1073/pnas.1318703111
DO - 10.1073/pnas.1318703111
M3 - Article
C2 - 24872444
AN - SCOPUS:84902134541
SN - 0027-8424
VL - 111
SP - 8535
EP - 8540
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23
ER -