Zooming in on disordered systems: Neutron reflection studies of proteins associated with fluid membranes

•Neutron reflection: a new tool for structural biology of membrane-associated proteins•Proteins characterized on fluid membranes, and disordered protein segments located•Advanced modeling and rigorous error analysis increase deduced information.•Protein membrane penetration determined with 5 Å precision, 1 Å for crystal structure•Orientation of proteins with known internal structure determined with high precision

Neutron reflectometry (NR) is an emerging experimental technique for the structural characterization of proteins interacting with fluid bilayer membranes under conditions that mimic closely the cellular environment. Thus, cellular processes can be emulated in artificial systems and their molecular basis studied by adding cellular components one at a time in a well-controlled environment while the resulting structures, or structural changes in response to external cues, are monitored with neutron reflection. In recent years, sample environments, data collection strategies and data analysis were continuously refined. The combination of these improvements increases the information which can be obtained from NR to an extent that enables structural characterization of protein–membrane complexes at a length scale that exceeds the resolution of the measurement by far. Ultimately, the combination of NR with molecular dynamics (MD) simulations can be used to cross-validate the results of the two techniques and provide atomic-scale structural models. This review discusses these developments in detail and demonstrates how they provide new windows into relevant biomedical problems. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.

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