Matches in SemOpenAlex for { <https://semopenalex.org/work/W2030584003> ?p ?o ?g. }
- W2030584003 abstract "The E2 subunit of the mitochondrial multienzyme pyruvate dehydrogenase complex (PDC-E2) is the major autoantigen in the liver disease, primary biliary cirrhosis (PBC). An epitope region which has been localized to amino acids 91-227 is believed to include the residue K173 to which is attached the lipoyl cofactor. We investigated structural features of this epitope region by screening random peptide phage-displayed libraries and identified prevalent phagotopes that contained likely contact amino acids in separate regions of the linear sequence, H132M133, and F178, V180. These were confirmed by site-directed alanine mutagenesis singly or in combination of the HM and FV residues in wild-type (wt) PDC-E2, and by immunization of rabbits with phage that expressed peptides MHLNTPP or FVLPWRI. The lipoyl lysine K173 also was mutated. Reactivities of mutants and wild-type (wt) PDC-E2, compared by ELISA using 12 PBC sera, showed decremental reactivity of mutant versus wt PDC-E2 (normalized to 100%): wt PDC-E2 (100%)>>PDC-E2(F178A,V180A) (mean+/-S.D., 59+/-17%)>PDC-E2(M133A) (50+/-13%)>PDC-E2(H132A) (36+/-13%)>PDC-E2(H132A,M133A) (28+/-8%)>PDC-E2(H132A,M133A,F178V,M180A) (18+/-13%). Notably PDC-E2(K173A) retained full reactivity (93+/-21%). Rabbits immunized with phage peptides generated antibodies reactive with entire PDC-E2. Our data convincingly validate phage library technology for defining spatially disparate contact residues for conformational epitopes. Ensuing data could be generally applicable to search for occult extrinsic agents as initiators of autoimmunity." @default.
- W2030584003 created "2016-06-24" @default.
- W2030584003 creator A5066321948 @default.
- W2030584003 creator A5073399902 @default.
- W2030584003 creator A5077761167 @default.
- W2030584003 date "2006-02-01" @default.
- W2030584003 modified "2023-09-24" @default.
- W2030584003 title "Amino acids critical for binding of autoantibody to an immunodominant conformational epitope of the pyruvate dehydrogenase complex subunit E2: Identification by phage display and site-directed mutagenesis" @default.
- W2030584003 cites W1483887312 @default.
- W2030584003 cites W1487704589 @default.
- W2030584003 cites W1583746545 @default.
- W2030584003 cites W1597163568 @default.
- W2030584003 cites W193034086 @default.
- W2030584003 cites W1946357118 @default.
- W2030584003 cites W1977048855 @default.
- W2030584003 cites W1986753195 @default.
- W2030584003 cites W1994675047 @default.
- W2030584003 cites W2000216967 @default.
- W2030584003 cites W2001194134 @default.
- W2030584003 cites W2003466408 @default.
- W2030584003 cites W2010029133 @default.
- W2030584003 cites W2010649076 @default.
- W2030584003 cites W2044421449 @default.
- W2030584003 cites W2046339687 @default.
- W2030584003 cites W2047069310 @default.
- W2030584003 cites W2051184695 @default.
- W2030584003 cites W2057906904 @default.
- W2030584003 cites W2058118684 @default.
- W2030584003 cites W2059674429 @default.
- W2030584003 cites W2061868451 @default.
- W2030584003 cites W2066726677 @default.
- W2030584003 cites W2072698880 @default.
- W2030584003 cites W2080938189 @default.
- W2030584003 cites W2082702784 @default.
- W2030584003 cites W2085454437 @default.
- W2030584003 cites W2093304786 @default.
- W2030584003 cites W2094439390 @default.
- W2030584003 cites W2096249455 @default.
- W2030584003 cites W2098041233 @default.
- W2030584003 cites W2104031636 @default.
- W2030584003 cites W2113530505 @default.
- W2030584003 cites W2119967316 @default.
- W2030584003 cites W2130054499 @default.
- W2030584003 cites W2160425610 @default.
- W2030584003 cites W2161124893 @default.
- W2030584003 cites W2171445832 @default.
- W2030584003 cites W4233725227 @default.
- W2030584003 cites W4234307110 @default.
- W2030584003 cites W4240099301 @default.
- W2030584003 doi "https://doi.org/10.1016/j.molimm.2005.03.011" @default.
- W2030584003 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16360019" @default.
- W2030584003 hasPublicationYear "2006" @default.
- W2030584003 type Work @default.
- W2030584003 sameAs 2030584003 @default.
- W2030584003 citedByCount "4" @default.
- W2030584003 countsByYear W20305840032013 @default.
- W2030584003 countsByYear W20305840032018 @default.
- W2030584003 crossrefType "journal-article" @default.
- W2030584003 hasAuthorship W2030584003A5066321948 @default.
- W2030584003 hasAuthorship W2030584003A5073399902 @default.
- W2030584003 hasAuthorship W2030584003A5077761167 @default.
- W2030584003 hasConcept C104292427 @default.
- W2030584003 hasConcept C104317684 @default.
- W2030584003 hasConcept C143065580 @default.
- W2030584003 hasConcept C153911025 @default.
- W2030584003 hasConcept C159654299 @default.
- W2030584003 hasConcept C16318435 @default.
- W2030584003 hasConcept C181199279 @default.
- W2030584003 hasConcept C185592680 @default.
- W2030584003 hasConcept C186268636 @default.
- W2030584003 hasConcept C195616568 @default.
- W2030584003 hasConcept C2779281246 @default.
- W2030584003 hasConcept C2780632150 @default.
- W2030584003 hasConcept C2781241564 @default.
- W2030584003 hasConcept C515207424 @default.
- W2030584003 hasConcept C54355233 @default.
- W2030584003 hasConcept C55493867 @default.
- W2030584003 hasConcept C86803240 @default.
- W2030584003 hasConcept C88099638 @default.
- W2030584003 hasConcept C9365378 @default.
- W2030584003 hasConceptScore W2030584003C104292427 @default.
- W2030584003 hasConceptScore W2030584003C104317684 @default.
- W2030584003 hasConceptScore W2030584003C143065580 @default.
- W2030584003 hasConceptScore W2030584003C153911025 @default.
- W2030584003 hasConceptScore W2030584003C159654299 @default.
- W2030584003 hasConceptScore W2030584003C16318435 @default.
- W2030584003 hasConceptScore W2030584003C181199279 @default.
- W2030584003 hasConceptScore W2030584003C185592680 @default.
- W2030584003 hasConceptScore W2030584003C186268636 @default.
- W2030584003 hasConceptScore W2030584003C195616568 @default.
- W2030584003 hasConceptScore W2030584003C2779281246 @default.
- W2030584003 hasConceptScore W2030584003C2780632150 @default.
- W2030584003 hasConceptScore W2030584003C2781241564 @default.
- W2030584003 hasConceptScore W2030584003C515207424 @default.
- W2030584003 hasConceptScore W2030584003C54355233 @default.
- W2030584003 hasConceptScore W2030584003C55493867 @default.
- W2030584003 hasConceptScore W2030584003C86803240 @default.
- W2030584003 hasConceptScore W2030584003C88099638 @default.
- W2030584003 hasConceptScore W2030584003C9365378 @default.
- W2030584003 hasLocation W20305840031 @default.