FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2754876693> ?p ?o ?g. }

• W2754876693 endingPage "18591" @default.
• W2754876693 startingPage "18577" @default.
• W2754876693 abstract "Dysferlin is a large transmembrane protein that plays a key role in cell membrane repair and underlies a recessive form of inherited muscular dystrophy. Dysferlinopathy is characterized by absence or marked reduction of dysferlin protein with 43% of reported pathogenic variants being missense variants that span the length of the dysferlin protein. The unique structure of dysferlin, with seven tandem C2 domains separated by linkers, suggests dysferlin may dynamically associate with phospholipid membranes in response to Ca2+ signaling. However, the overall conformation of the dysferlin protein is uncharacterized. To dissect the structural architecture of dysferlin, we have applied the method of limited proteolysis, which allows nonspecific digestion of unfolded peptides by trypsin. Using five antibodies spanning the dysferlin protein, we identified a highly reproducible jigsaw map of dysferlin fragments protected from digestion. Our data infer a modular architecture of four tertiary domains: 1) C2A, which is readily removed as a solo domain; 2) midregion C2B-C2C-Fer-DysF, commonly excised as an intact module, with subdigestion to different fragments suggesting several dynamic folding options; 3) C-terminal four-C2 domain module; and 4) calpain-cleaved mini-dysferlinC72, which is particularly resistant to proteolysis. Importantly, we reveal a patient missense variant, L344P, that largely escapes proteasomal surveillance and shows subtle but clear changes in tertiary conformation. Accompanying evidence from immunohistochemistry and flow cytometry using antibodies with conformationally sensitive epitopes supports proteolysis data. Collectively, we provide insight into the structural topology of dysferlin and show how a single missense mutation within dysferlin can exert local changes in tertiary conformation." @default.
• W2754876693 created "2017-09-25" @default.
• W2754876693 creator A5003438809 @default.
• W2754876693 creator A5008811325 @default.
• W2754876693 creator A5010795211 @default.
• W2754876693 creator A5046631277 @default.
• W2754876693 creator A5046695853 @default.
• W2754876693 creator A5052350687 @default.
• W2754876693 creator A5053165850 @default.
• W2754876693 creator A5081617758 @default.
• W2754876693 date "2017-11-01" @default.
• W2754876693 modified "2023-10-14" @default.
• W2754876693 title "Limited proteolysis as a tool to probe the tertiary conformation of dysferlin and structural consequences of patient missense variant L344P" @default.
• W2754876693 cites W1551910894 @default.
• W2754876693 cites W1592698849 @default.
• W2754876693 cites W1607813252 @default.
• W2754876693 cites W1809106246 @default.
• W2754876693 cites W1970692622 @default.
• W2754876693 cites W1979880724 @default.
• W2754876693 cites W1983351039 @default.
• W2754876693 cites W1991817429 @default.
• W2754876693 cites W1992083670 @default.
• W2754876693 cites W1993325764 @default.
• W2754876693 cites W1995057697 @default.
• W2754876693 cites W2013270869 @default.
• W2754876693 cites W2036657040 @default.
• W2754876693 cites W2039847498 @default.
• W2754876693 cites W2041098512 @default.
• W2754876693 cites W2043172254 @default.
• W2754876693 cites W2043222731 @default.
• W2754876693 cites W2047136624 @default.
• W2754876693 cites W2056566809 @default.
• W2754876693 cites W2065940519 @default.
• W2754876693 cites W2071162640 @default.
• W2754876693 cites W2073797769 @default.
• W2754876693 cites W2074784562 @default.
• W2754876693 cites W2083380993 @default.
• W2754876693 cites W2086036400 @default.
• W2754876693 cites W2093925869 @default.
• W2754876693 cites W2102958109 @default.
• W2754876693 cites W2106514785 @default.
• W2754876693 cites W2106862730 @default.
• W2754876693 cites W2109931578 @default.
• W2754876693 cites W2112697515 @default.
• W2754876693 cites W2114243513 @default.
• W2754876693 cites W2116629782 @default.
• W2754876693 cites W2121781519 @default.
• W2754876693 cites W2132087763 @default.
• W2754876693 cites W2133067061 @default.
• W2754876693 cites W2136422440 @default.
• W2754876693 cites W2137392137 @default.
• W2754876693 cites W2140197284 @default.
• W2754876693 cites W2146097739 @default.
• W2754876693 cites W2151034762 @default.
• W2754876693 cites W2154100802 @default.
• W2754876693 cites W2161973949 @default.
• W2754876693 cites W2168335394 @default.
• W2754876693 cites W2226584831 @default.
• W2754876693 cites W2267675678 @default.
• W2754876693 cites W2283639878 @default.
• W2754876693 cites W2320395894 @default.
• W2754876693 doi "https://doi.org/10.1074/jbc.m117.790014" @default.
• W2754876693 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5682967" @default.
• W2754876693 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28904177" @default.
• W2754876693 hasPublicationYear "2017" @default.
• W2754876693 type Work @default.
• W2754876693 sameAs 2754876693 @default.
• W2754876693 citedByCount "6" @default.
• W2754876693 countsByYear W27548766932019 @default.
• W2754876693 countsByYear W27548766932020 @default.
• W2754876693 countsByYear W27548766932022 @default.
• W2754876693 countsByYear W27548766932023 @default.
• W2754876693 crossrefType "journal-article" @default.
• W2754876693 hasAuthorship W2754876693A5003438809 @default.
• W2754876693 hasAuthorship W2754876693A5008811325 @default.
• W2754876693 hasAuthorship W2754876693A5010795211 @default.
• W2754876693 hasAuthorship W2754876693A5046631277 @default.
• W2754876693 hasAuthorship W2754876693A5046695853 @default.
• W2754876693 hasAuthorship W2754876693A5052350687 @default.
• W2754876693 hasAuthorship W2754876693A5053165850 @default.
• W2754876693 hasAuthorship W2754876693A5081617758 @default.
• W2754876693 hasBestOaLocation W27548766931 @default.
• W2754876693 hasConcept C104317684 @default.
• W2754876693 hasConcept C181199279 @default.
• W2754876693 hasConcept C185592680 @default.
• W2754876693 hasConcept C2781307694 @default.
• W2754876693 hasConcept C37113945 @default.
• W2754876693 hasConcept C501734568 @default.
• W2754876693 hasConcept C54355233 @default.
• W2754876693 hasConcept C55493867 @default.
• W2754876693 hasConcept C71924100 @default.
• W2754876693 hasConcept C75563809 @default.
• W2754876693 hasConcept C75599170 @default.
• W2754876693 hasConcept C86803240 @default.
• W2754876693 hasConceptScore W2754876693C104317684 @default.
• W2754876693 hasConceptScore W2754876693C181199279 @default.
• W2754876693 hasConceptScore W2754876693C185592680 @default.
• W2754876693 hasConceptScore W2754876693C2781307694 @default.

• next