A fine balance of hydrophobic-electrostatic communication pathways in a pH-switching protein.

ABSTRACT: Allostery is the phenomenon of coupling between distal binding sites in a protein. Such coupling is at the crux of protein function and regulation in a myriad of scenarios, yet determining the molecular mechanisms of coupling networks in proteins remains a major challenge. Here, we report mechanisms governing pH-dependent myristoyl switching in monomeric hisactophilin, whereby the myristoyl moves between a sequestered state, i.e., buried within the core of the protein, to an accessible state, in which the myristoyl has increased accessibility for membrane binding. Measurements of the pH and temperature dependence of amide chemical shifts reveal protein local structural stability and conformational heterogeneity that accompany switching. An analysis of these measurements using a thermodynam

SUBMITTER: MacKenzie DWS 

PROVIDER: S-EPMC9245636 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature