Probing the energy barriers and stages of membrane protein unfolding using solid-state NMR spectroscopy.

ABSTRACT: Understanding how the amino acid sequence dictates protein structure and defines its stability is a fundamental problem in molecular biology. It is especially challenging for membrane proteins that reside in the complex environment of a lipid bilayer. Here, we obtain an atomic-level picture of the thermally induced unfolding of a membrane-embedded α-helical protein, human aquaporin 1, using solid-state nuclear magnetic resonance spectroscopy. Our data reveal the hierarchical two-step pathway that begins with unfolding of a structured extracellular loop and proceeds to an intermediate state with a native-like helical packing. In the second step, the transmembrane domain unravels as a single unit, resulting in a heterogeneous misfolded state with high helical content but with nonnative helic

SUBMITTER: Xiao P 

PROVIDER: S-EPMC11639674 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature