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Publication Abstract from PubMed

Protein structures are dynamic, undergoing motions that can play a vital role in function. However, the link between primary sequence and conformational dynamics remains poorly understood. Here, we studied how conformational dynamics can arise in a globular protein by evaluating the impact of individual core-residue substitutions in DANCER-3, a streptococcal protein G domain beta1 variant that we previously designed to undergo a specific mode of conformational exchange that has never been observed in the wild-type protein. Using a combination of solution NMR experiments and molecular dynamics simulations, we demonstrate that only two mutations are necessary to create this conformational exchange, and that these mutations work synergistically, with one destabilizing the native structure and the other allowing two new conformational states to be accessed on the energy landscape. Overall, our results show how dynamics can appear in a stable globular fold, a critical step in the molecular evolution of dynamics-linked functions.

Origin of conformational dynamics in a globular protein.,Damry AM, Mayer MM, Broom A, Goto NK, Chica RA Commun Biol. 2019 Nov 26;2:433. doi: 10.1038/s42003-019-0681-2. eCollection 2019. PMID:31799435^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.