FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3111426004> ?p ?o ?g. }

• W3111426004 endingPage "186" @default.
• W3111426004 startingPage "185" @default.
• W3111426004 abstract "Membranes have long been known to serve multiple critical roles for cells, including acting as barriers and also as gatekeepers, controlling the flow of materials and information between the cell and the exterior environment. More recently, it has been realized that membranes also act as sensors, responding to mechanical stimuli through modulation of the behavior of a growing number of identified membrane-embedded proteins in all domains of life. Chief among these proteins are so-called mechanosensitive (MS) ion channels, some of which can open under a change in membrane tension. The existence of MS channels was first recognized in auditory hair cells (1Corey D.P. Hudspeth A.J. Ionic basis of the receptor potential in a vertebrate hair cell.Nature. 1979; 281: 675-677Crossref PubMed Scopus (350) Google Scholar) and in embryonic chick skeletal muscle (2Guharay F. Sachs F. Stretch-activated single ion channel currents in tissue-cultured embryonic chick skeletal muscle.J. Physiol. 1984; 352: 685-701Crossref PubMed Scopus (693) Google Scholar). They were later discovered in bacteria as well (3Martinac B. Buechner M. Kung C. et al.Pressure-sensitive ion channel in Escherichia coli.Proc. Natl. Acad. Sci. USA. 1987; 84: 2297-2301Crossref PubMed Scopus (507) Google Scholar), where they allow these organisms to avoid bursting under the sudden increases in turgor pressure that might occur during, e.g., rainfall by rapidly (within milliseconds) releasing osmolytes from the cell (4Kung C. A possible unifying principle for mechanosensation.Nature. 2005; 436: 647-654Crossref PubMed Scopus (468) Google Scholar). The first few structures of MS channels were determined in the late 1990s and early 2000s, namely the mechanosensitive channel of large conductance (MscL) and small conductance (MscS) (Fig. 1). Molecular dynamics (MD) simulations were soon after carried out by a number of groups in an attempt to understand how the channels are affected by application of tension, looking particularly for the gating transitions between closed and open states (5Colombo G. Marrink S.J. Mark A.E. Simulation of MscL gating in a bilayer under stress.Biophys. J. 2003; 84: 2331-2337Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar, 6Gullingsrud J. Schulten K. Gating of MscL studied by steered molecular dynamics.Biophys. J. 2003; 85: 2087-2099Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar, 7Sotomayor M. Schulten K. Molecular dynamics study of gating in the mechanosensitive channel of small conductance MscS.Biophys. J. 2004; 87: 3050-3065Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar, 8Anishkin A. Sukharev S. Water dynamics and dewetting transitions in the small mechanosensitive channel MscS.Biophys. J. 2004; 86: 2883-2895Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar). The most common computational approach to induce a transition to the open state has been the direct application of external forces to the protein (6Gullingsrud J. Schulten K. Gating of MscL studied by steered molecular dynamics.Biophys. J. 2003; 85: 2087-2099Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar,9Jeon J. Voth G.A. Gating of the mechanosensitive channel protein MscL: the interplay of membrane and protein.Biophys. J. 2008; 94: 3497-3511Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar) or of tension to the membrane (5Colombo G. Marrink S.J. Mark A.E. Simulation of MscL gating in a bilayer under stress.Biophys. J. 2003; 84: 2331-2337Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar,10Yefimov S. van der Giessen E. Marrink S.J. et al.Mechanosensitive membrane channels in action.Biophys. J. 2008; 94: 2994-3002Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar). However, because the simulation timescale (ns) was typically less than the timescale of gating (μs–ms), large forces or tensions were required, making the resulting conformational changes of the proteins open to interpretation. In this issue of Biophysical Journal, Vanegas and colleagues report on a novel approach to generating realistic gating transitions of MS channels in MD simulations, overcoming the limitations normally inherent to the disparate timescales (11Rajeshwar T.R. Anishkin A. Vanegas J.M. et al.Mechanical activation of MscL revealed by a locally distributed tension molecular dynamics approach.Biophys. J. 2021; 120: 232-242Google Scholar). Called locally distributed tension MD (LDT-MD), the approach applies forces to the lipids surrounding the protein; these forces rapidly decay with increasing radial distance from the center of the protein. By applying forces primarily to lipids near the protein, the authors circumvent the inefficiency of force transmission through the softer membrane to the stiffer protein while still capturing the interactions between the two that facilitate gating. They apply LDT-MD to MscL, and within just a few nanoseconds, they are able to generate reversible opening of the pore. In contrast, applying tension to the entire membrane either did not open the pore, ruptured the membrane, or both. Structural properties of the LDT-MD-generated open state of MscL were found to agree with experiments. Taking the method further, the authors combine LDT-MD with metadynamics, determining the free energy as a function of the change in area at different effective membrane tensions; yet again, the open state of MscL matches experimental expectations. In a final example, they demonstrate that LDT-MD can also be used to generate asymmetric forces in the two leaflets, mimicking, e.g., the addition of lysolipids to one leaflet. Comparison with distances measured in FRET experiments reveals a counterintuitive result, namely that adding lysolipids to one side of the membrane causes expansion rather than compression on that side. The ability to capture the effects of mechanical stimuli on membranes and membrane proteins in MD simulations is needed as much now as it was 15–20 years ago. In addition to the bacterial MS ion channels, eukaryotic MS channels are now being characterized and simulated, e.g., vertebrate Piezo channels (Fig. 1; (12Coste B. Mathur J. Patapoutian A. et al.Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels.Science. 2010; 330: 55-60Crossref PubMed Scopus (1067) Google Scholar,13Botello-Smith W.M. Jiang W. Luo Y. et al.A mechanism for the activation of the mechanosensitive Piezo1 channel by the small molecule Yoda1.Nat. Commun. 2019; 10: 4503Crossref PubMed Scopus (33) Google Scholar)), plant OSCA channels (14Zhang M. Wang D. Chen L. et al.Structure of the mechanosensitive OSCA channels.Nat. Struct. Mol. Biol. 2018; 25: 850-858Crossref PubMed Scopus (49) Google Scholar), and others (15Kefauver J.M. Ward A.B. Patapoutian A. Discoveries in structure and physiology of mechanically activated ion channels.Nature. 2020; 587: 567-576Crossref PubMed Scopus (37) Google Scholar). The mechanical properties of other membranes are also of significant interest, such as the Gram-negative bacterial outer membrane (16Hwang H. Paracini N. Gumbart J.C. et al.Distribution of mechanical stress in the Escherichia coli cell envelope.Biochim. Biophys. Acta Biomembr. 2018; 1860: 2566-2575Crossref PubMed Scopus (40) Google Scholar, 17Rojas E.R. Billings G. Huang K.C. et al.The outer membrane is an essential load-bearing element in Gram-negative bacteria.Nature. 2018; 559: 617-621Crossref PubMed Scopus (158) Google Scholar, 18Lessen H.J. Fleming P.J. Sodt A.J. et al.Building blocks of the outer membrane: calculating a general elastic energy model for β-barrel membrane proteins.J. Chem. Theory Comput. 2018; 14: 4487-4497Crossref PubMed Scopus (12) Google Scholar). Simulations of all of these systems will benefit from novel approaches such as LDT-MD. J.C.G. acknowledges support from the National Institutes of Health ( R01-GM123169 )." @default.
• W3111426004 created "2020-12-21" @default.
• W3111426004 creator A5080510232 @default.
• W3111426004 date "2021-01-01" @default.
• W3111426004 modified "2023-09-27" @default.
• W3111426004 title "A Novel Approach to Simulating the Gating Transitions of Mechanosensitive Channels" @default.
• W3111426004 cites W1988378570 @default.
• W3111426004 cites W1997766063 @default.
• W3111426004 cites W1999720993 @default.
• W3111426004 cites W2012608189 @default.
• W3111426004 cites W2059865583 @default.
• W3111426004 cites W2071195125 @default.
• W3111426004 cites W2083517980 @default.
• W3111426004 cites W2086354121 @default.
• W3111426004 cites W2125942201 @default.
• W3111426004 cites W2131223624 @default.
• W3111426004 cites W2144791518 @default.
• W3111426004 cites W2842578025 @default.
• W3111426004 cites W2884934298 @default.
• W3111426004 cites W2893857764 @default.
• W3111426004 cites W2979208253 @default.
• W3111426004 cites W3109143003 @default.
• W3111426004 cites W3111487926 @default.
• W3111426004 cites W4250222110 @default.
• W3111426004 doi "https://doi.org/10.1016/j.bpj.2020.12.004" @default.
• W3111426004 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7840399" @default.
• W3111426004 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33382974" @default.
• W3111426004 hasPublicationYear "2021" @default.
• W3111426004 type Work @default.
• W3111426004 sameAs 3111426004 @default.
• W3111426004 citedByCount "0" @default.
• W3111426004 crossrefType "journal-article" @default.
• W3111426004 hasAuthorship W3111426004A5080510232 @default.
• W3111426004 hasBestOaLocation W31114260041 @default.
• W3111426004 hasConcept C121332964 @default.
• W3111426004 hasConcept C12554922 @default.
• W3111426004 hasConcept C127162648 @default.
• W3111426004 hasConcept C170493617 @default.
• W3111426004 hasConcept C185592680 @default.
• W3111426004 hasConcept C194544171 @default.
• W3111426004 hasConcept C31258907 @default.
• W3111426004 hasConcept C4001165 @default.
• W3111426004 hasConcept C41008148 @default.
• W3111426004 hasConcept C50254741 @default.
• W3111426004 hasConcept C55493867 @default.
• W3111426004 hasConcept C86803240 @default.
• W3111426004 hasConceptScore W3111426004C121332964 @default.
• W3111426004 hasConceptScore W3111426004C12554922 @default.
• W3111426004 hasConceptScore W3111426004C127162648 @default.
• W3111426004 hasConceptScore W3111426004C170493617 @default.
• W3111426004 hasConceptScore W3111426004C185592680 @default.
• W3111426004 hasConceptScore W3111426004C194544171 @default.
• W3111426004 hasConceptScore W3111426004C31258907 @default.
• W3111426004 hasConceptScore W3111426004C4001165 @default.
• W3111426004 hasConceptScore W3111426004C41008148 @default.
• W3111426004 hasConceptScore W3111426004C50254741 @default.
• W3111426004 hasConceptScore W3111426004C55493867 @default.
• W3111426004 hasConceptScore W3111426004C86803240 @default.
• W3111426004 hasFunder F4320332161 @default.
• W3111426004 hasIssue "2" @default.
• W3111426004 hasLocation W31114260041 @default.
• W3111426004 hasLocation W31114260042 @default.
• W3111426004 hasLocation W31114260043 @default.
• W3111426004 hasOpenAccess W3111426004 @default.
• W3111426004 hasPrimaryLocation W31114260041 @default.
• W3111426004 hasRelatedWork W2014573882 @default.
• W3111426004 hasRelatedWork W2464564128 @default.
• W3111426004 hasRelatedWork W2991601256 @default.
• W3111426004 hasRelatedWork W3132617828 @default.
• W3111426004 hasRelatedWork W3217390172 @default.
• W3111426004 hasRelatedWork W331524620 @default.
• W3111426004 hasRelatedWork W4309046853 @default.
• W3111426004 hasRelatedWork W4319936555 @default.
• W3111426004 hasRelatedWork W52090877 @default.
• W3111426004 hasRelatedWork W269528509 @default.
• W3111426004 hasVolume "120" @default.
• W3111426004 isParatext "false" @default.
• W3111426004 isRetracted "false" @default.
• W3111426004 magId "3111426004" @default.
• W3111426004 workType "article" @default.