New Horizons in Structural Biology of Membrane Proteins: Experimental Evaluation of the Role of Conformational Dynamics and Intrinsic Flexibility

Membranes

Olga Vinogradova¹  Eric T. Christenson²  Robbins Puthenveetil³ 

[1] Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA;OriGene Technologies, Inc., Rockville, MD 20850, USA;Section on Structural and Chemical Biology of Membrane Proteins, Neurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 35A Convent Dr., Bethesda, MD 20892, USA;

关键词: membrane proteins;    membrane protein structure;    membrane protein dynamics;    NMR;    cryo-EM;    X-ray;   

DOI  :  10.3390/membranes12020227

来源: DOAJ

【 摘 要 】

A plethora of membrane proteins are found along the cell surface and on the convoluted labyrinth of membranes surrounding organelles. Since the advent of various structural biology techniques, a sub-population of these proteins has become accessible to investigation at near-atomic resolutions. The predominant bona fide methods for structure solution, X-ray crystallography and cryo-EM, provide high resolution in three-dimensional space at the cost of neglecting protein motions through time. Though structures provide various rigid snapshots, only an amorphous mechanistic understanding can be inferred from interpolations between these different static states. In this review, we discuss various techniques that have been utilized in observing dynamic conformational intermediaries that remain elusive from rigid structures. More specifically we discuss the application of structural techniques such as NMR, cryo-EM and X-ray crystallography in studying protein dynamics along with complementation by conformational trapping by specific binders such as antibodies. We finally showcase the strength of various biophysical techniques including FRET, EPR and computational approaches using a multitude of succinct examples from GPCRs, transporters and ion channels.

【 授权许可】

Unknown