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Article: Structural analysis of the UBA domain of x-linked inhibitor of apoptosis protein reveals different surfaces for ubiquitin-binding and self-association

TitleStructural analysis of the UBA domain of x-linked inhibitor of apoptosis protein reveals different surfaces for ubiquitin-binding and self-association
Authors
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS one, 2011, v. 6 n. 12, article no. e28511 How to Cite?
AbstractBACKGROUND: Inhibitor of apoptosis proteins (IAPs) belong to a pivotal antiapoptotic protein family that plays a crucial role in tumorigenesis, cancer progression, chemoresistance and poor patient-survival. X-linked inhibitor of apoptosis protein (XIAP) is a prominent member of IAPs attracting intense research because it has been demonstrated to be a physiological inhibitor of caspases and apoptosis. Recently, an evolutionarily conserved ubiquitin-associated (UBA) domain was identified in XIAP and a number of RING domain-bearing IAPs. This has placed the IAPs in the group of ubiquitin binding proteins. Here, we explore the three-dimensional structure of the XIAP UBA domain (XIAP-UBA) and how it interacts with mono-ubiquitin and diubiquitin conjugates. PRINCIPAL FINDINGS: The solution structure of the XIAP-UBA domain was determined by NMR spectroscopy. XIAP-UBA adopts a typical UBA domain fold of three tightly packed alpha-helices but with an additional N-terminal 3(10) helix. The XIAP-UBA binds mono-ubiquitin as well as Lys48-linked and linear-linked diubiquitins at low-micromolar affinities. NMR analysis of the XIAP-UBA-ubiquitin interaction reveals that it involves the classical hydrophobic patches surrounding Ile44 of ubiquitin and the conserved MGF/LV motif surfaces on XIAP-UBA. Furthermore, dimerization of XIAP-UBA was observed. Mapping of the self-association surface of XIAP-UBA reveals that the dimerization interface is formed by residues in the N-terminal 3(10) helix, helix alpha1 and helix alpha2, separate from the ubiquitin-binding surface. CONCLUSION: Our results provide the first structural information of XIAP-UBA and map its interaction with mono-ubiquitin, Lys48-linked and linear-linked diubiquitins. The notion that XIAP-UBA uses different surfaces for ubiquitin-binding and self-association provides a plausible model to explain the reported selectivity of XIAP in binding polyubiquitin chains with different linkages.
Persistent Identifierhttp://hdl.handle.net/10722/157661
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTse, MKen_US
dc.contributor.authorHui, SKen_US
dc.contributor.authorYang, YHen_US
dc.contributor.authorYin, STen_US
dc.contributor.authorHu, HYen_US
dc.contributor.authorZou, Ben_US
dc.contributor.authorWong, BCYen_US
dc.contributor.authorSze, KHen_US
dc.date.accessioned2012-08-08T08:52:02Z-
dc.date.available2012-08-08T08:52:02Z-
dc.date.issued2011en_US
dc.identifier.citationPLoS one, 2011, v. 6 n. 12, article no. e28511en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10722/157661-
dc.description.abstractBACKGROUND: Inhibitor of apoptosis proteins (IAPs) belong to a pivotal antiapoptotic protein family that plays a crucial role in tumorigenesis, cancer progression, chemoresistance and poor patient-survival. X-linked inhibitor of apoptosis protein (XIAP) is a prominent member of IAPs attracting intense research because it has been demonstrated to be a physiological inhibitor of caspases and apoptosis. Recently, an evolutionarily conserved ubiquitin-associated (UBA) domain was identified in XIAP and a number of RING domain-bearing IAPs. This has placed the IAPs in the group of ubiquitin binding proteins. Here, we explore the three-dimensional structure of the XIAP UBA domain (XIAP-UBA) and how it interacts with mono-ubiquitin and diubiquitin conjugates. PRINCIPAL FINDINGS: The solution structure of the XIAP-UBA domain was determined by NMR spectroscopy. XIAP-UBA adopts a typical UBA domain fold of three tightly packed alpha-helices but with an additional N-terminal 3(10) helix. The XIAP-UBA binds mono-ubiquitin as well as Lys48-linked and linear-linked diubiquitins at low-micromolar affinities. NMR analysis of the XIAP-UBA-ubiquitin interaction reveals that it involves the classical hydrophobic patches surrounding Ile44 of ubiquitin and the conserved MGF/LV motif surfaces on XIAP-UBA. Furthermore, dimerization of XIAP-UBA was observed. Mapping of the self-association surface of XIAP-UBA reveals that the dimerization interface is formed by residues in the N-terminal 3(10) helix, helix alpha1 and helix alpha2, separate from the ubiquitin-binding surface. CONCLUSION: Our results provide the first structural information of XIAP-UBA and map its interaction with mono-ubiquitin, Lys48-linked and linear-linked diubiquitins. The notion that XIAP-UBA uses different surfaces for ubiquitin-binding and self-association provides a plausible model to explain the reported selectivity of XIAP in binding polyubiquitin chains with different linkages.en_US
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_US
dc.relation.ispartofPLoS oneen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAmino Acid Sequence-
dc.subject.meshLysine - metabolism-
dc.subject.meshMagnetic Resonance Spectroscopy-
dc.subject.meshUbiquitin - metabolism-
dc.subject.meshX-Linked Inhibitor of Apoptosis Protein - chemistry - metabolism-
dc.titleStructural analysis of the UBA domain of x-linked inhibitor of apoptosis protein reveals different surfaces for ubiquitin-binding and self-associationen_US
dc.typeArticleen_US
dc.identifier.emailTse, MK: bctmk@hkucc.hku.hken_US
dc.identifier.emailHui, SK: h0238870@hkusua.hku.hken_US
dc.identifier.emailZou, B: zoubing@hkucc.hku.hk-
dc.identifier.emailWong, BCY: bcywong@hku.hk-
dc.identifier.emailSze, KH: khsze@hku.hk-
dc.identifier.authorityWong, BCY=rp00429en_US
dc.identifier.authoritySze, KH=rp00785en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0028511en_US
dc.identifier.pmid22194841-
dc.identifier.pmcidPMC3240630-
dc.identifier.scopuseid_2-s2.0-83455262533en_US
dc.identifier.hkuros211864-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-83455262533&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume6en_US
dc.identifier.issue12, article no. e28511en_US
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000298370400015-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridSze, KH=7006735061en_US
dc.identifier.scopusauthoridWong, BCY=7402023340en_US
dc.identifier.scopusauthoridZou, B=35228257300en_US
dc.identifier.scopusauthoridHu, HY=16312758800en_US
dc.identifier.scopusauthoridYin, ST=24069335300en_US
dc.identifier.scopusauthoridYang, Y=35750932800en_US
dc.identifier.scopusauthoridHui, SK=13406279000en_US
dc.identifier.scopusauthoridTse, MK=36437795000en_US

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