Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Lee, Juhwan | - |
dc.contributor.author | Sim, Kyoung Mi | - |
dc.contributor.author | Kang, Mooseok | - |
dc.contributor.author | Oh, Hyun Ju | - |
dc.contributor.author | Choi, Ho Jung | - |
dc.contributor.author | Kim, Yeong Eun | - |
dc.contributor.author | Pack, Chan-Gi | - |
dc.contributor.author | Kim, Kyunggon | - |
dc.contributor.author | Kim, Kyung Mo | - |
dc.contributor.author | Oh, Seak Hee | - |
dc.contributor.author | Kim, Inki | - |
dc.contributor.author | Chang, Iksoo | - |
dc.date.accessioned | 2024-02-21T10:10:16Z | - |
dc.date.available | 2024-02-21T10:10:16Z | - |
dc.date.created | 2024-01-19 | - |
dc.date.issued | 2024-01 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/47972 | - |
dc.description.abstract | X-linked inhibitor of apoptosis protein (XIAP) deficiency causes refractory inflammatory bowel disease. The XIAP protein plays a pivotal role in the pro-inflammatory response through the nucleotide-binding oligomerization domain-containing signaling pathway that is important in mucosal homeostasis. We analyzed the molecular mechanism of non-synonymous pathogenic variants (PVs) of XIAP BIR2 domain. We generated N-terminally green fluorescent protein-tagged XIAP constructs of representative non-synonymous PVs. Co-immunoprecipitation and fluorescence cross-correlation spectroscopy showed that wild-type XIAP and RIP2 preferentially interacted in live cells, whereas all non-synonymous PV XIAPs failed to interact properly with RIP2. Structural analysis showed that various structural changes by mutations, such as hydrophobic core collapse, Zn-finger loss, and spatial rearrangement, destabilized the two loop structures (174–182 and 205–215) that critically interact with RIP2. Subsequently, it caused a failure of RIP2 ubiquitination and loss of protein deficiency by the auto-ubiquitination of all XIAP mutants. These findings could enhance our understanding of the role of XIAP mutations in XIAP-deficient inflammatory bowel disease and may benefit future therapeutic strategies. © 2024, The Author(s). | - |
dc.language | English | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Understanding the molecular mechanism of pathogenic variants of BIR2 domain in XIAP-deficient inflammatory bowel disease | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/s41598-023-50932-5 | - |
dc.identifier.scopusid | 2-s2.0-85181700440 | - |
dc.identifier.bibliographicCitation | Scientific Reports, v.14, no.1 | - |
dc.description.isOpenAccess | TRUE | - |
dc.subject.keywordPlus | X-LINKED INHIBITOR | - |
dc.subject.keywordPlus | ZINC-FINGER | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | DYNAMICS | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | SYNCHRONIZATION | - |
dc.subject.keywordPlus | SIMULATIONS | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | IAPS | - |
dc.citation.number | 1 | - |
dc.citation.title | Scientific Reports | - |
dc.citation.volume | 14 | - |