Matches in SemOpenAlex for { <https://semopenalex.org/work/W4254788191> ?p ?o ?g. }
Showing items 1 to 67 of
67
with 100 items per page.
- W4254788191 endingPage "253a" @default.
- W4254788191 startingPage "253a" @default.
- W4254788191 abstract "Cellular inhibitor of apoptosis 1 (cIAP1) is an E3 ubiquitin ligase with roles in both apoptosis and NF-κB signaling. Recent crystallographic and SAXS data have shown that the ligase activity of cIAP1 is autoinhibited by occlusion of the RING dimerization interface through several inter-domain interactions, most critically in the BIR3:RING interface. This interaction is disrupted by SMAC and SMAC mimetics, initiating cIAP1 dimerization through its newly exposed RING domain and activation of its E3 ligase activity. Activation of cIAP1's ligase activity leads to cIAP1 autoubiquitination and proteasomal degradation. Intriguingly, we observed that although the binding site for cIAP1's E2 partner enzyme is occluded in the crystal structure, E2 binds to both the monomeric and dimeric forms of cIAP1 with nearly the same affinity. This unexpected result indicated that there were likely significant residual motions occurring within monomeric cIAP1. Through NMR relaxation dispersion measurements and resonance broadening we have been able to detect significant motions occurring on relatively fast, microsecond-millisecond timescales at specific domain interfaces present in the autoinhibited form of cIAP1. In addition, time-resolved SAXS measurements conducted in line with a stopped flow injection system have allowed us to measure the opening rate of cIAP1, which occurs over hundreds of milliseconds. The tight regulation of apoptosis is essential in multicellular organisms and the proteins involved in transducing pro-apoptotic and anti-apoptotic signals are no doubt under stringent evolutionary control. The internal motions present in cIAP1 likely arose from the competing pressures to activate apoptosis as quickly as possible while maintaining the fidelity of the pro-apoptotic signal." @default.
- W4254788191 created "2022-05-12" @default.
- W4254788191 creator A5003716440 @default.
- W4254788191 creator A5007397829 @default.
- W4254788191 creator A5009946597 @default.
- W4254788191 creator A5017301570 @default.
- W4254788191 creator A5044566453 @default.
- W4254788191 creator A5074774307 @default.
- W4254788191 date "2014-01-01" @default.
- W4254788191 modified "2023-10-18" @default.
- W4254788191 title "Internal Motions Prime cIAP1 for Rapid Activation" @default.
- W4254788191 doi "https://doi.org/10.1016/j.bpj.2013.11.1490" @default.
- W4254788191 hasPublicationYear "2014" @default.
- W4254788191 type Work @default.
- W4254788191 citedByCount "0" @default.
- W4254788191 crossrefType "journal-article" @default.
- W4254788191 hasAuthorship W4254788191A5003716440 @default.
- W4254788191 hasAuthorship W4254788191A5007397829 @default.
- W4254788191 hasAuthorship W4254788191A5009946597 @default.
- W4254788191 hasAuthorship W4254788191A5017301570 @default.
- W4254788191 hasAuthorship W4254788191A5044566453 @default.
- W4254788191 hasAuthorship W4254788191A5074774307 @default.
- W4254788191 hasBestOaLocation W42547881911 @default.
- W4254788191 hasConcept C104317684 @default.
- W4254788191 hasConcept C12554922 @default.
- W4254788191 hasConcept C134459356 @default.
- W4254788191 hasConcept C175114707 @default.
- W4254788191 hasConcept C181199279 @default.
- W4254788191 hasConcept C185592680 @default.
- W4254788191 hasConcept C25602115 @default.
- W4254788191 hasConcept C47701112 @default.
- W4254788191 hasConcept C55493867 @default.
- W4254788191 hasConcept C8010536 @default.
- W4254788191 hasConcept C86803240 @default.
- W4254788191 hasConcept C95444343 @default.
- W4254788191 hasConceptScore W4254788191C104317684 @default.
- W4254788191 hasConceptScore W4254788191C12554922 @default.
- W4254788191 hasConceptScore W4254788191C134459356 @default.
- W4254788191 hasConceptScore W4254788191C175114707 @default.
- W4254788191 hasConceptScore W4254788191C181199279 @default.
- W4254788191 hasConceptScore W4254788191C185592680 @default.
- W4254788191 hasConceptScore W4254788191C25602115 @default.
- W4254788191 hasConceptScore W4254788191C47701112 @default.
- W4254788191 hasConceptScore W4254788191C55493867 @default.
- W4254788191 hasConceptScore W4254788191C8010536 @default.
- W4254788191 hasConceptScore W4254788191C86803240 @default.
- W4254788191 hasConceptScore W4254788191C95444343 @default.
- W4254788191 hasIssue "2" @default.
- W4254788191 hasLocation W42547881911 @default.
- W4254788191 hasOpenAccess W4254788191 @default.
- W4254788191 hasPrimaryLocation W42547881911 @default.
- W4254788191 hasRelatedWork W132581103 @default.
- W4254788191 hasRelatedWork W1988820070 @default.
- W4254788191 hasRelatedWork W2040509817 @default.
- W4254788191 hasRelatedWork W2070509485 @default.
- W4254788191 hasRelatedWork W2078031314 @default.
- W4254788191 hasRelatedWork W2332083897 @default.
- W4254788191 hasRelatedWork W3109816058 @default.
- W4254788191 hasRelatedWork W3212834903 @default.
- W4254788191 hasRelatedWork W4212875242 @default.
- W4254788191 hasRelatedWork W4295897835 @default.
- W4254788191 hasVolume "106" @default.
- W4254788191 isParatext "false" @default.
- W4254788191 isRetracted "false" @default.
- W4254788191 workType "article" @default.