Year: 2025
Type: article
Abstract: Substrate transport through membrane transporters is a dynamic process that involves transitions between different functional conformations, which can be disrupted by non-native membrane mimetics. Capturing these conformations and their transitions within native cellular membranes presents a notable challenge. Herein, we used in situ solid-state nuclear magnetic resonance (NMR) to resolve the 1.5-Å outward-open and 2.5-Å occluded structures of Bj SemiSWEET within its native cellular membranes. Our findings reveal that these two conformations exchange within transmembrane helix TM1 and Loop L2-3 on a millisecond to second timescale, with the exchange rate corresponding to the sucrose transport rate. Molecular dynamics simulations further confirmed that these conformations represent functional states during sucrose transport. In contrast, we observed different conformational dynamics of Bj SemiSWEET in DMPC/DMPG synthetic bilayers compared to cellular membranes. This study highlights the potential of in situ solid-state NMR to provide previously unknown dynamic structural insights into cellular molecular processes, representing a substantial advancement in dynamic cellular structural biology.
Source: Science Advances
Institutions: Wuhan Institute of Physics and Mathematics, Wuhan University of Science and Technology, Innovation Academy for Precision Measurement Science and Technology, CAS, State Key Laboratory of Refractories and Metallurgy, University of Chinese Academy of Sciences, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W4416203142