6NJF

Solution NMR Structure of DANCER3-F34A, a rigid and natively folded single mutant of the dynamic protein DANCER-3

Summary for 6NJF

• Entry DOI: 10.2210/pdb6njf/pdb
• NMR Information: BMRB: 30532
• Descriptor: Immunoglobulin G-binding protein G (1 entity in total)
• Functional Keywords: dynamics, computational design, conformational exchange, immunoglobulin-binding, de novo protein
• Biological source: Streptococcus sp. group G
• Total number of polymer chains: 1
• Total formula weight: 7230.96

Authors

Damry, A.M.,Mayer, M.M.,Goto, N.K.,Chica, R.A. (deposition date: 2019-01-03, release date: 2019-08-21, Last modification date: 2024-05-15)

Primary citation

Damry, A.M.,Mayer, M.M.,Broom, A.,Goto, N.K.,Chica, R.A.
Origin of conformational dynamics in a globular protein.
Commun Biol, 2:433-433, 2019

PubMed Abstract: 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 β1 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.

PubMed: 31799435
DOI: 10.1038/s42003-019-0681-2

Experimental method

SOLUTION NMR