Abstract
A growing number of integral membrane proteins have been shown to tune their activity by selectively interacting with specific lipids. The ability to regulate biological functions via lipid interactions extends to the diverse group of proteins that associate only peripherally with the lipid bilayer. However, the structural basis of these interactions remains challenging to study due to their transient and promiscuous nature. Recently, native mass spectrometry has come into focus as a new tool to investigate lipid interactions in membrane proteins. Here, we outline how the native MS strategies developed for integral membrane proteins can be applied to generate insights into the structure and function of peripheral membrane proteins. Specifically, native MS studies of proteins in complex with detergent-solubilized lipids, bound to lipid nanodiscs, and released from native-like lipid vesicles all shed new light on the role of lipid interactions. The unique ability of native MS to capture and interrogate protein–protein, protein–ligand, and protein–lipid interactions opens exciting new avenues for the study of peripheral membrane protein biology.
Highlights
Lipid membranes provide a multitude of crucial functions for the cell
Native mass spectrometry has come into focus as a new tool to investigate lipid interactions in membrane proteins
They enable the existence of segregated, controlled chemical milieus by acting as a physical barrier to the outside and between subcellular compartments. They control the passage of nutrients, cellular components, and signals, facilitated by a myriad of membrane-associated proteins. This membrane proteome can be divided into integral membrane proteins, which contain multiple membrane-spanning segments and extend into both cytoplasm and extracellular space, and peripheral membrane proteins, which insert only partially into the hydrophobic core of the membrane, or associate with the lipid head-groups at its surface, but remain largely in the hydrophilic environment [1]
Summary
Scratching the surface: native mass spectrometry of peripheral membrane protein complexes. A growing number of integral membrane proteins have been shown to tune their activity by selectively interacting with specific lipids. The ability to regulate biological functions via lipid interactions extends to the diverse group of proteins that associate only peripherally with the lipid bilayer. Native mass spectrometry has come into focus as a new tool to investigate lipid interactions in membrane proteins. Native MS studies of proteins in complex with detergent-solubilized lipids, bound to lipid nanodiscs, and released from native-like lipid vesicles all shed new light on the role of lipid interactions. The unique ability of native MS to capture and interrogate protein–protein, protein–ligand, and protein–lipid interactions opens exciting new avenues for the study of peripheral membrane protein biology
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
