Folding pathways of proteins with increasing degree of sequence identities but different structure and function. - Archive ouverte HAL Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2012

Folding pathways of proteins with increasing degree of sequence identities but different structure and function.

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Abstract

Much experimental work has been devoted in comparing the folding behavior of proteins sharing the same fold but different sequence. The recent design of proteins displaying very high sequence identities but different 3D structure allows the unique opportunity to address the protein-folding problem from a complementary perspective. Here we explored by Φ-value analysis the pathways of folding of three different heteromorphic pairs, displaying increasingly high-sequence identity (namely, 30%, 77%, and 88%), but different structures called G(A) (a 3-α helix fold) and G(B) (an α/β fold). The analysis, based on 132 site-directed mutants, is fully consistent with the idea that protein topology is committed very early along the pathway of folding. Furthermore, data reveals that when folding approaches a perfect two-state scenario, as in the case of the G(A) domains, the structural features of the transition state appear very robust to changes in sequence composition. On the other hand, when folding is more complex and multistate, as for the G(B)s, there are alternative nuclei or accessible pathways that can be alternatively stabilized by altering the primary structure. The implications of our results in the light of previous work on the folding of different members belonging to the same protein family are discussed.
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Dates and versions

pasteur-00960063 , version 1 (17-03-2014)

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Rajanish Giri, Angela Morrone, Carlo Travaglini-Allocatelli, Per Jemth, Maurizio Brunori, et al.. Folding pathways of proteins with increasing degree of sequence identities but different structure and function.. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109 (44), pp.17772-6. ⟨10.1073/pnas.1201794109⟩. ⟨pasteur-00960063⟩

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