2021
DOI: 10.1007/s00232-020-00165-8
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Tracking Membrane Protein Dynamics in Real Time

Abstract: Membrane proteins govern critical cellular processes and are central to human health and associated disease. Understanding of membrane protein function is obscured by the vast ranges of structural dynamics—both in the spatial and time regime—displayed in the protein and surrounding membrane. The membrane lipids have emerged as allosteric modulators of membrane protein function, which further adds to the complexity. In this review, we discuss several examples of membrane dependency. A particular focus is on how… Show more

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Cited by 16 publications
(10 citation statements)
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“…The TR-XSS methodology is optimal for tracking conformational dynamics in real time and determines cooperativity and ordering of structural events ( 58 ). To obtain a measurable signal, a large population of protein molecules needs to be triggered to synchronize their functional conformation dynamics in time.…”
Section: Discussionmentioning
confidence: 99%
“…The TR-XSS methodology is optimal for tracking conformational dynamics in real time and determines cooperativity and ordering of structural events ( 58 ). To obtain a measurable signal, a large population of protein molecules needs to be triggered to synchronize their functional conformation dynamics in time.…”
Section: Discussionmentioning
confidence: 99%
“…With the widespread use of rapid x-ray detectors at synchrotron radiation sources 43 and the development of appropriate microfluidic mixing technologies for reaction initiation, it should become possible to extend the field of different XSS studies of integral membrane proteins to incorporate protein and substrate or reagent mixing studies to initiate time-resolved studies. Since caged compounds have also been successfully used for such studies, 28,29 the sub-field of TR-XSS has the potential to grow beyond the study of naturally light-driven systems. Because all future experimental developments require solid theoretical foundations and because the detergent micelle may itself be influenced by mixing, the analysis tools and fitting protocols developed here should provide a framework that allows the field to look to the future with confidence.…”
Section: Discussionmentioning
confidence: 99%
“…The lipid membrane is involved in crucial protein-mediated cellular processes that include protein sorting, transport, and signaling. Structurally, the lipid membrane is categorized as a surface characterized by a strong hydrophobic core and electrostatic surface that can constitute heterogeneous microstructures including lipid rafts. Such chemical demarcation influences a protein’s dynamical interaction with lipid membrane and, further, alters protein conformations along with membrane topology. Generally, the dynamics of a membrane protein is greatly reduced as compared to cytosolic proteins. Again, membrane anisotropy causes slower rotational diffusion in proteins than translational diffusion.…”
Section: Perturbative Effects and Biological Consequencesmentioning
confidence: 99%
“…Furthermore, advancements in enhanced sampling algorithms along with powerful computational architectures are allowing the computation of free energy landscapes for membrane protein dynamics, helping in understanding their mechanisms at molecular details. 209,212 Volume exclusion, compartmentalization of cellular components, and organization of organelles are the manifestations of cellular confinement. 213−215 In biology, confinement has significant effects on phenomena ranging from protein folding to viral replication.…”
Section: ■ Introductionmentioning
confidence: 99%