FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912257634> ?p ?o ?g. }

• W2912257634 endingPage "1425" @default.
• W2912257634 startingPage "1409" @default.
• W2912257634 abstract "Protein aggregation is the underlying cause of many diseases, and also limits the usefulness of many natural and engineered proteins in biotechnology. Better mechanistic understanding and characterization of aggregation-prone states is needed to guide protein engineering, formulation, and drug-targeting strategies that prevent aggregation. While several final aggregated states—notably amyloids—have been characterized structurally, very little is known about the native structural conformers that initiate aggregation. We used a novel combination of small-angle x-ray scattering (SAXS), atomistic molecular dynamic simulations, single-molecule Förster resonance energy transfer, and aggregation-prone region predictions, to characterize structural changes in a native humanized Fab A33 antibody fragment, that correlated with the experimental aggregation kinetics. SAXS revealed increases in the native state radius of gyration, Rg, of 2.2% to 4.1%, at pH 5.5 and below, concomitant with accelerated aggregation. In a cutting-edge approach, we fitted the SAXS data to full MD simulations from the same conditions and located the conformational changes in the native state to the constant domain of the light chain (CL). This CL displacement was independently confirmed using single-molecule Förster resonance energy transfer measurements with two dual-labeled Fabs. These conformational changes were also found to increase the solvent exposure of a predicted APR, suggesting a likely mechanism through which they promote aggregation. Our findings provide a means by which aggregation-prone conformational states can be readily determined experimentally, and thus potentially used to guide protein engineering, or ligand binding strategies, with the aim of stabilizing the protein against aggregation." @default.
• W2912257634 created "2019-02-21" @default.
• W2912257634 creator A5001133461 @default.
• W2912257634 creator A5006865539 @default.
• W2912257634 creator A5055548278 @default.
• W2912257634 creator A5061856293 @default.
• W2912257634 creator A5065002639 @default.
• W2912257634 creator A5067740300 @default.
• W2912257634 creator A5085397116 @default.
• W2912257634 date "2019-03-01" @default.
• W2912257634 modified "2023-10-16" @default.
• W2912257634 title "An Expanded Conformation of an Antibody Fab Region by X-Ray Scattering, Molecular Dynamics, and smFRET Identifies an Aggregation Mechanism" @default.
• W2912257634 cites W1031578623 @default.
• W2912257634 cites W1581858536 @default.
• W2912257634 cites W1970898345 @default.
• W2912257634 cites W1971281089 @default.
• W2912257634 cites W1972260684 @default.
• W2912257634 cites W1972638614 @default.
• W2912257634 cites W1985147004 @default.
• W2912257634 cites W1985941856 @default.
• W2912257634 cites W1986826865 @default.
• W2912257634 cites W1990736367 @default.
• W2912257634 cites W1992243940 @default.
• W2912257634 cites W1994323576 @default.
• W2912257634 cites W1998045383 @default.
• W2912257634 cites W1999248724 @default.
• W2912257634 cites W2005279391 @default.
• W2912257634 cites W2009962980 @default.
• W2912257634 cites W2014875724 @default.
• W2912257634 cites W2015557312 @default.
• W2912257634 cites W2016876962 @default.
• W2912257634 cites W2024028394 @default.
• W2912257634 cites W2027839322 @default.
• W2912257634 cites W2033853317 @default.
• W2912257634 cites W2040619626 @default.
• W2912257634 cites W2043614254 @default.
• W2912257634 cites W2043876754 @default.
• W2912257634 cites W2049827200 @default.
• W2912257634 cites W2053727980 @default.
• W2912257634 cites W2053951161 @default.
• W2912257634 cites W2054881399 @default.
• W2912257634 cites W2063096624 @default.
• W2912257634 cites W2066000489 @default.
• W2912257634 cites W2067608620 @default.
• W2912257634 cites W2074443308 @default.
• W2912257634 cites W2074726906 @default.
• W2912257634 cites W2080831965 @default.
• W2912257634 cites W2080880014 @default.
• W2912257634 cites W2081640562 @default.
• W2912257634 cites W2086938888 @default.
• W2912257634 cites W2094052190 @default.
• W2912257634 cites W2107036307 @default.
• W2912257634 cites W2115237582 @default.
• W2912257634 cites W2116711646 @default.
• W2912257634 cites W2117020466 @default.
• W2912257634 cites W2128485227 @default.
• W2912257634 cites W2133425057 @default.
• W2912257634 cites W2141654481 @default.
• W2912257634 cites W2142740016 @default.
• W2912257634 cites W2142844453 @default.
• W2912257634 cites W2148313902 @default.
• W2912257634 cites W2149636054 @default.
• W2912257634 cites W2152997175 @default.
• W2912257634 cites W2157873167 @default.
• W2912257634 cites W2160544821 @default.
• W2912257634 cites W2163266294 @default.
• W2912257634 cites W2164361934 @default.
• W2912257634 cites W2165186407 @default.
• W2912257634 cites W2224827007 @default.
• W2912257634 cites W2228872279 @default.
• W2912257634 cites W2279088384 @default.
• W2912257634 cites W2327631209 @default.
• W2912257634 cites W2396487155 @default.
• W2912257634 cites W2411303265 @default.
• W2912257634 cites W2411462566 @default.
• W2912257634 cites W2412542910 @default.
• W2912257634 cites W2614053601 @default.
• W2912257634 cites W2619641367 @default.
• W2912257634 cites W2769321120 @default.
• W2912257634 cites W2774294088 @default.
• W2912257634 cites W2782758955 @default.
• W2912257634 cites W2808570070 @default.
• W2912257634 cites W2950138311 @default.
• W2912257634 doi "https://doi.org/10.1016/j.jmb.2019.02.009" @default.
• W2912257634 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30776431" @default.
• W2912257634 hasPublicationYear "2019" @default.
• W2912257634 type Work @default.
• W2912257634 sameAs 2912257634 @default.
• W2912257634 citedByCount "18" @default.
• W2912257634 countsByYear W29122576342019 @default.
• W2912257634 countsByYear W29122576342020 @default.
• W2912257634 countsByYear W29122576342021 @default.
• W2912257634 countsByYear W29122576342022 @default.
• W2912257634 countsByYear W29122576342023 @default.
• W2912257634 crossrefType "journal-article" @default.
• W2912257634 hasAuthorship W2912257634A5001133461 @default.
• W2912257634 hasAuthorship W2912257634A5006865539 @default.
• W2912257634 hasAuthorship W2912257634A5055548278 @default.

• next