Correlation of membrane protein conformational and functional dynamics. Academic Article uri icon

Overview

abstract

  • Conformational changes in ion channels lead to gating of an ion-conductive pore. Ion flux has been measured with high temporal resolution by single-channel electrophysiology for decades. However, correlation between functional and conformational dynamics remained difficult, lacking experimental techniques to monitor sub-millisecond conformational changes. Here, we use the outer membrane protein G (OmpG) as a model system where loop-6 opens and closes the β-barrel pore like a lid in a pH-dependent manner. Functionally, single-channel electrophysiology shows that while closed states are favored at acidic pH and open states are favored at physiological pH, both states coexist and rapidly interchange in all conditions. Using HS-AFM height spectroscopy (HS-AFM-HS), we monitor sub-millisecond loop-6 conformational dynamics, and compare them to the functional dynamics from single-channel recordings, while MD simulations provide atomistic details and energy landscapes of the pH-dependent loop-6 fluctuations. HS-AFM-HS offers new opportunities to analyze conformational dynamics at timescales of domain and loop fluctuations.

publication date

  • July 16, 2021

Research

keywords

  • Bacterial Outer Membrane Proteins
  • Electrophysiology
  • Escherichia coli
  • Escherichia coli Proteins
  • Ion Channels
  • Porins

Identity

PubMed Central ID

  • PMC8285522

Scopus Document Identifier

  • 85110713923

Digital Object Identifier (DOI)

  • 10.1016/S0006-3495(87)83298-8

PubMed ID

  • 34272395

Additional Document Info

volume

  • 12

issue

  • 1