Matches in SemOpenAlex for { <https://semopenalex.org/work/W3127973521> ?p ?o ?g. }
- W3127973521 endingPage "1715" @default.
- W3127973521 startingPage "1705" @default.
- W3127973521 abstract "Human γD (HγD) and γC (HγC) are two-domain crystallin (Crys) proteins expressed in the nucleus of the eye lens. Structural perturbations in the protein often trigger aggregation, which eventually leads to cataract. To decipher the underlying molecular mechanism, it is important to characterize the partially unfolded conformations, which are aggregation-prone. Using a coarse grained protein model and molecular dynamics simulations, we studied the role of on-pathway folding intermediates in the early stages of aggregation. The multidimensional free energy surface revealed at least three different folding pathways with the population of partially structured intermediates. The two dominant pathways confirm sequential folding of the N-terminal [Ntd] and the C-terminal domains [Ctd], while the third, least favored, pathway involves intermediates where both the domains are partially folded. A native-like intermediate (I*), featuring the folded domains and disrupted interdomain contacts, gets populated in all three pathways. I* forms domain swapped dimers by swapping the entire Ntds and Ctds with other monomers. Population of such oligomers can explain the increased resistance to unfolding resulting in hysteresis observed in the folding experiments of HγD Crys. An ensemble of double domain swapped dimers are also formed during refolding, where intermediates consisting of partially folded Ntds and Ctds swap secondary structures with other monomers. The double domain swapping model presented in our study provides structural insights into the early events of aggregation in Crys proteins and identifies the key secondary structural swapping elements, where introducing mutations will aid in regulating the overall aggregation propensity." @default.
- W3127973521 created "2021-02-15" @default.
- W3127973521 creator A5075084768 @default.
- W3127973521 creator A5075379669 @default.
- W3127973521 creator A5081904017 @default.
- W3127973521 date "2021-02-10" @default.
- W3127973521 modified "2023-10-16" @default.
- W3127973521 title "Double Domain Swapping in Human γC and γD Crystallin Drives Early Stages of Aggregation" @default.
- W3127973521 cites W1490241380 @default.
- W3127973521 cites W1539653122 @default.
- W3127973521 cites W1591864042 @default.
- W3127973521 cites W1974229917 @default.
- W3127973521 cites W1974409885 @default.
- W3127973521 cites W1978012062 @default.
- W3127973521 cites W1978206480 @default.
- W3127973521 cites W1979761607 @default.
- W3127973521 cites W1980956149 @default.
- W3127973521 cites W1985388329 @default.
- W3127973521 cites W1989925383 @default.
- W3127973521 cites W1995543945 @default.
- W3127973521 cites W1997261132 @default.
- W3127973521 cites W1998234601 @default.
- W3127973521 cites W2000374333 @default.
- W3127973521 cites W2001987122 @default.
- W3127973521 cites W2018459217 @default.
- W3127973521 cites W2027266392 @default.
- W3127973521 cites W2028445408 @default.
- W3127973521 cites W2030345298 @default.
- W3127973521 cites W2031908838 @default.
- W3127973521 cites W2032185892 @default.
- W3127973521 cites W2032652519 @default.
- W3127973521 cites W2033546129 @default.
- W3127973521 cites W2037320703 @default.
- W3127973521 cites W2039961720 @default.
- W3127973521 cites W2040743789 @default.
- W3127973521 cites W2044031095 @default.
- W3127973521 cites W2044339391 @default.
- W3127973521 cites W2045820581 @default.
- W3127973521 cites W2046684890 @default.
- W3127973521 cites W2048596414 @default.
- W3127973521 cites W2051086233 @default.
- W3127973521 cites W2052092359 @default.
- W3127973521 cites W2054930616 @default.
- W3127973521 cites W2058203258 @default.
- W3127973521 cites W2058713258 @default.
- W3127973521 cites W2060367452 @default.
- W3127973521 cites W2061107874 @default.
- W3127973521 cites W2090586240 @default.
- W3127973521 cites W2092853815 @default.
- W3127973521 cites W2097617033 @default.
- W3127973521 cites W2103598875 @default.
- W3127973521 cites W2109610280 @default.
- W3127973521 cites W2111855120 @default.
- W3127973521 cites W2112154906 @default.
- W3127973521 cites W2113461670 @default.
- W3127973521 cites W2119675439 @default.
- W3127973521 cites W2122538666 @default.
- W3127973521 cites W2132103632 @default.
- W3127973521 cites W2132938122 @default.
- W3127973521 cites W2134616947 @default.
- W3127973521 cites W2137053539 @default.
- W3127973521 cites W2140918764 @default.
- W3127973521 cites W2141862035 @default.
- W3127973521 cites W2145101544 @default.
- W3127973521 cites W2155537965 @default.
- W3127973521 cites W2156698698 @default.
- W3127973521 cites W2159175420 @default.
- W3127973521 cites W2160082320 @default.
- W3127973521 cites W2160788743 @default.
- W3127973521 cites W2164028467 @default.
- W3127973521 cites W2178481958 @default.
- W3127973521 cites W2209466135 @default.
- W3127973521 cites W2240530368 @default.
- W3127973521 cites W2322685908 @default.
- W3127973521 cites W2462180543 @default.
- W3127973521 cites W2465646024 @default.
- W3127973521 cites W2486872289 @default.
- W3127973521 cites W2556136530 @default.
- W3127973521 cites W2610933635 @default.
- W3127973521 cites W2891468774 @default.
- W3127973521 cites W2903620025 @default.
- W3127973521 cites W2912414400 @default.
- W3127973521 cites W2951095848 @default.
- W3127973521 cites W2951103176 @default.
- W3127973521 cites W2955969736 @default.
- W3127973521 cites W2968670330 @default.
- W3127973521 cites W2973275620 @default.
- W3127973521 cites W3100773375 @default.
- W3127973521 cites W3104054400 @default.
- W3127973521 doi "https://doi.org/10.1021/acs.jpcb.0c07833" @default.
- W3127973521 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33566611" @default.
- W3127973521 hasPublicationYear "2021" @default.
- W3127973521 type Work @default.
- W3127973521 sameAs 3127973521 @default.
- W3127973521 citedByCount "1" @default.
- W3127973521 countsByYear W31279735212023 @default.
- W3127973521 crossrefType "journal-article" @default.
- W3127973521 hasAuthorship W3127973521A5075084768 @default.