Matches in SemOpenAlex for { <https://semopenalex.org/work/W4233381607> ?p ?o ?g. }
- W4233381607 endingPage "8667" @default.
- W4233381607 startingPage "8654" @default.
- W4233381607 abstract "Multicellular organisms consist of cells that interact via elaborate adhesion complexes. Desmosomes are membrane-associated adhesion complexes that mechanically tether the cytoskeletal intermediate filaments (IFs) between two adjacent cells, creating a network of tough connections in tissues such as skin and heart. Desmoplakin (DP) is the key desmosomal protein that binds IFs, and the DP·IF association poses a quandary: desmoplakin must stably and tightly bind IFs to maintain the structural integrity of the desmosome. Yet, newly synthesized DP must traffic along the cytoskeleton to the site of nascent desmosome assembly without “sticking” to the IF network, implying weak or transient DP···IF contacts. Recent work reveals that these contacts are modulated by post-translational modifications (PTMs) in DP’s C-terminal tail (DPCTT). Using molecular dynamics simulations, we have elucidated the structural basis of these PTM-induced effects. Our simulations, nearing 2 μs in aggregate, indicate that phosphorylation of S2849 induces an “arginine claw” in desmoplakin’s C-terminal tail. If a key arginine, R2834, is methylated, the DPCTT preferentially samples conformations that are geometrically well-suited as substrates for processive phosphorylation by the cognate kinase GSK3. We suggest that DPCTT is a molecular switch that modulates, via its conformational dynamics, DP’s overall efficacy as a substrate for GSK3. Finally, we show that the fluctuating DPCTT can contact other parts of DP, suggesting a competitive binding mechanism for the modulation of DP···IF interactions." @default.
- W4233381607 created "2022-05-12" @default.
- W4233381607 creator A5006428391 @default.
- W4233381607 creator A5022761529 @default.
- W4233381607 date "2016-06-03" @default.
- W4233381607 modified "2023-09-25" @default.
- W4233381607 title "Claws, Disorder, and Conformational Dynamics of the C-Terminal Region of Human Desmoplakin" @default.
- W4233381607 cites W1620204708 @default.
- W4233381607 cites W1646941628 @default.
- W4233381607 cites W1770349940 @default.
- W4233381607 cites W1833591189 @default.
- W4233381607 cites W1847844380 @default.
- W4233381607 cites W1952317074 @default.
- W4233381607 cites W1964296596 @default.
- W4233381607 cites W1966431081 @default.
- W4233381607 cites W1968991415 @default.
- W4233381607 cites W1970103851 @default.
- W4233381607 cites W1972376083 @default.
- W4233381607 cites W1974077096 @default.
- W4233381607 cites W1974750165 @default.
- W4233381607 cites W1975915682 @default.
- W4233381607 cites W1977675356 @default.
- W4233381607 cites W1978714931 @default.
- W4233381607 cites W1979546184 @default.
- W4233381607 cites W1982677458 @default.
- W4233381607 cites W1984481443 @default.
- W4233381607 cites W1988810304 @default.
- W4233381607 cites W1991820295 @default.
- W4233381607 cites W1997151511 @default.
- W4233381607 cites W1998602609 @default.
- W4233381607 cites W1998982727 @default.
- W4233381607 cites W2000358808 @default.
- W4233381607 cites W2003240840 @default.
- W4233381607 cites W2005001379 @default.
- W4233381607 cites W2007213164 @default.
- W4233381607 cites W2007905703 @default.
- W4233381607 cites W2022950330 @default.
- W4233381607 cites W2026760312 @default.
- W4233381607 cites W2027408247 @default.
- W4233381607 cites W2028766225 @default.
- W4233381607 cites W2029667189 @default.
- W4233381607 cites W2033136849 @default.
- W4233381607 cites W2033782813 @default.
- W4233381607 cites W2036581153 @default.
- W4233381607 cites W2036858312 @default.
- W4233381607 cites W2037778125 @default.
- W4233381607 cites W2037948240 @default.
- W4233381607 cites W2040452705 @default.
- W4233381607 cites W2040809566 @default.
- W4233381607 cites W2047427411 @default.
- W4233381607 cites W2049073062 @default.
- W4233381607 cites W2053227378 @default.
- W4233381607 cites W2060872117 @default.
- W4233381607 cites W2066609609 @default.
- W4233381607 cites W2070753604 @default.
- W4233381607 cites W2076049773 @default.
- W4233381607 cites W2076142854 @default.
- W4233381607 cites W2077130771 @default.
- W4233381607 cites W2081204899 @default.
- W4233381607 cites W2081300509 @default.
- W4233381607 cites W2085822999 @default.
- W4233381607 cites W2088650216 @default.
- W4233381607 cites W2089258285 @default.
- W4233381607 cites W2100088353 @default.
- W4233381607 cites W2103819633 @default.
- W4233381607 cites W2117399884 @default.
- W4233381607 cites W2121374178 @default.
- W4233381607 cites W2125520334 @default.
- W4233381607 cites W2130493552 @default.
- W4233381607 cites W2141707814 @default.
- W4233381607 cites W2144062946 @default.
- W4233381607 cites W2150981663 @default.
- W4233381607 cites W2154714625 @default.
- W4233381607 cites W2158937675 @default.
- W4233381607 cites W2160105296 @default.
- W4233381607 cites W2168721191 @default.
- W4233381607 cites W2169851453 @default.
- W4233381607 cites W2234602429 @default.
- W4233381607 cites W2270353826 @default.
- W4233381607 cites W2294569491 @default.
- W4233381607 cites W2318815774 @default.
- W4233381607 cites W2327651587 @default.
- W4233381607 cites W2331500237 @default.
- W4233381607 cites W3100104164 @default.
- W4233381607 cites W39042124 @default.
- W4233381607 cites W4232058283 @default.
- W4233381607 doi "https://doi.org/10.1021/acs.jpcb.6b03261" @default.
- W4233381607 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27188911" @default.
- W4233381607 hasPublicationYear "2016" @default.
- W4233381607 type Work @default.
- W4233381607 citedByCount "5" @default.
- W4233381607 countsByYear W42333816072018 @default.
- W4233381607 countsByYear W42333816072019 @default.
- W4233381607 countsByYear W42333816072023 @default.
- W4233381607 crossrefType "journal-article" @default.
- W4233381607 hasAuthorship W4233381607A5006428391 @default.
- W4233381607 hasAuthorship W4233381607A5022761529 @default.
- W4233381607 hasBestOaLocation W42333816072 @default.