Abstract
Biological membranes define the boundaries of cells and compartmentalize the chemical and physical processes required for life. Many biological processes are carried out by proteins embedded in or associated with such membranes. Determination of membrane protein (MP) structures at atomic or near-atomic resolution plays a vital role in elucidating their structural and functional impact in biology. This endeavor has determined 1198 unique MP structures as of early 2021. The value of these structures is expanded greatly by deposition of their three-dimensional (3D) coordinates into the Protein Data Bank (PDB) after the first atomic MP structure was elucidated in 1985. Since then, free access to MP structures facilitates broader and deeper understanding of MPs, which provides crucial new insights into their biological functions. Here we highlight the structural and functional biology of representative MPs and landmarks in the evolution of new technologies, with insights into key developments influenced by the PDB in magnifying their impact.
Highlights
Depended on the discovery of new technologies required for structural studies of membrane, versus soluble proteins
In the following Historical perspective, we provide a brief historical perspective of some membrane protein (MP) insights (other than the crucial G-protein-coupled receptors (GPCRs) that are the subject of a dedicated review in this volume) and consider the value of the Protein Data Bank (PDB) in disseminating this information
The structural biology of MPs has provided remarkable insights into the architecture and mechanisms of action of channels, transporters, pumps, and receptors and elucidated key aspects of the molecular machinery involved in their biogenesis: from the targeting and sorting as they emerge from the ribosome until their translocation across or insertion into biological membranes
Summary
Biological membranes define the boundaries of cells and compartmentalize the chemical and physical processes required for life. Determination of membrane protein (MP) structures at atomic or near-atomic resolution plays a vital role in elucidating their structural and functional impact in biology This endeavor has determined 1198 unique MP structures as of early 2021. We highlight the structural and functional biology of representative MPs and landmarks in the evolution of new technologies, with insights into key developments influenced by the PDB in magnifying their impact. In How do membrane proteins accomplish key physiological functions?, we describe how the structures of several of the major MP classes were uncovered, which often required technological developments that are woven into the fabric of structural biology. Some exciting developments in MP engineering focus on channelrhodopsins where light can trigger cellular responses and engineered dopamine sensors We hope that this necessarily limited perspective on the impact of selected MP structure classes may encourage opportunities in a broader context. We hope to communicate the value of MPs as guardians of the health of cells and how their structures, through the PDB, contribute important insights into many crucial aspects of physiology
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