Mechanistic Picture for Chemomechanical Coupling in a Bacterial Proton-Coupled Oligopeptide Transporter from Streptococcus Thermophilus

Immadisetty, Kalyan; Moradi, Mahmoud

doi:10.1021/acs.jpcb.1c03982

Cited by 3 publications

(3 citation statements)

References 51 publications

(137 reference statements)

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“…There are a number of studies and reviews on how cholesterol modulates class A GPCRs, but this area of study is yet to be fully explored for class C GPCRs. Recent advances in experimental and computational power have enabled researchers to investigate the role of lipids in various membranes and solvable proteins, at the atomic level using molecular dynamics simulation [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Cholesterol in Class C GPCRs: Role, Relevance, and Localization

et al. 2023

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G-protein coupled receptors (GPCRs), one of the largest superfamilies of cell-surface receptors, are heptahelical integral membrane proteins that play critical roles in virtually every organ system. G-protein-coupled receptors operate in membranes rich in cholesterol, with an imbalance in cholesterol level within the vicinity of GPCR transmembrane domains affecting the structure and/or function of many GPCRs, a phenomenon that has been linked to several diseases. These effects of cholesterol could result in indirect changes by altering the mechanical properties of the lipid environment or direct changes by binding to specific sites on the protein. There are a number of studies and reviews on how cholesterol modulates class A GPCRs; however, this area of study is yet to be explored for class C GPCRs, which are characterized by a large extracellular region and often form constitutive dimers. This review highlights specific sites of interaction, functions, and structural dynamics involved in the cholesterol recognition of the class C GPCRs. We summarize recent data from some typical family members to explain the effects of membrane cholesterol on the structural features and functions of class C GPCRs and speculate on their corresponding therapeutic potential.

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Section: Introductionmentioning

confidence: 99%

Cholesterol in Class C GPCRs: Role, Relevance, and Localization

et al. 2023

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Section: Introductionmentioning

confidence: 99%

Cholesterol in Class C GPCRs: Role, Relevance, and Localization

Isu¹,

Badiee²,

Khodadadi³

et al. 2023

Preprint

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G-protein coupled receptors (GPCRs), one of the largest superfamilies of cell-surface receptors, are heptahelical integral membrane proteins that play critical roles in virtually every organ system. G-protein-coupled receptors operate in membranes rich in cholesterol, with an imbalance in cholesterol level within the vicinity of GPCR transmembrane domains affecting the structure and/or function of many GPCRs, a phenomenon that has been linked to several diseases. These effects of cholesterol could result in indirect changes by altering the mechanical properties of the lipid environment or direct changes by binding to specific sites on the protein. There are a number of studies and reviews on how cholesterol modulates class A GPCRs, however, this area of study is yet to be explored for class C GPCRs, which are characterized by a large extracellular region and often form constitutive dimers. This review highlights specific sites of interaction, functions, and structural dynamics involved in the cholesterol recognition of the class C GPCRs. We summarize recent data from some typical family members to explain the effects of membrane cholesterol on the structural features and functions of Class C GPCRs and speculate on their corresponding therapeutic potential.

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“…MD is a powerful computational tool that is used, among other things, to study various therapeutically important targets at an atomic level [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] . Several MD studies using coarse-grained MD [41] , [42] , [43] or biased MD [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , have been conducted thus far for studying the activation of wild-type (WT) MscL.…”

Section: Introductionmentioning

confidence: 99%