Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206

Handle URI:
http://hdl.handle.net/10754/334484
Title:
Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206
Authors:
Liang, Yu; Huimei Hong, Felicia; Ganesan, Pugalenthi; Jiang, Sizun; Jauch, Ralf; Stanton, Lawrence W.; Kolatkar, Prasanna R.
Abstract:
Zfp206 (also named as Zscan10) belongs to the subfamily of C2H2 zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C2H2 transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development. 2012 The Author(s).
KAUST Department:
Biosciences Core Lab
Citation:
Liang Y, Huimei Hong F, Ganesan P, Jiang S, Jauch R, et al. (2012) Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206. Nucleic Acids Research 40: 8721-8732. doi:10.1093/nar/gks611.
Publisher:
Oxford University Press
Journal:
Nucleic Acids Research
Issue Date:
26-Jun-2012
DOI:
10.1093/nar/gks611
PubMed ID:
22735705
PubMed Central ID:
PMC3458555
Type:
Article
ISSN:
03051048
Appears in Collections:
Articles; Biosciences Core Lab

Full metadata record

DC FieldValue Language
dc.contributor.authorLiang, Yuen
dc.contributor.authorHuimei Hong, Feliciaen
dc.contributor.authorGanesan, Pugalenthien
dc.contributor.authorJiang, Sizunen
dc.contributor.authorJauch, Ralfen
dc.contributor.authorStanton, Lawrence W.en
dc.contributor.authorKolatkar, Prasanna R.en
dc.date.accessioned2014-11-11T14:27:05Z-
dc.date.available2014-11-11T14:27:05Z-
dc.date.issued2012-06-26en
dc.identifier.citationLiang Y, Huimei Hong F, Ganesan P, Jiang S, Jauch R, et al. (2012) Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206. Nucleic Acids Research 40: 8721-8732. doi:10.1093/nar/gks611.en
dc.identifier.issn03051048en
dc.identifier.pmid22735705en
dc.identifier.doi10.1093/nar/gks611en
dc.identifier.urihttp://hdl.handle.net/10754/334484en
dc.description.abstractZfp206 (also named as Zscan10) belongs to the subfamily of C2H2 zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C2H2 transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development. 2012 The Author(s).en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0en
dc.subjectprotein Zfp206en
dc.subjecttranscription factoren
dc.subjectunclassified drugen
dc.subjectamino terminal sequenceen
dc.subjectarticleen
dc.subjectcomplex formationen
dc.subjectcontrolled studyen
dc.subjectcrystal structureen
dc.subjectdimerizationen
dc.subjectembryonic stem cellen
dc.subjectenhancer regionen
dc.subjectgene deletionen
dc.subjectgene mutationen
dc.subjectimmunoprecipitationen
dc.subjectin vitro studyen
dc.subjectmolecular biologyen
dc.subjectnonhumanen
dc.subjectpriority journalen
dc.subjectprotein analysisen
dc.subjectprotein bindingen
dc.subjectprotein domainen
dc.subjectprotein expressionen
dc.subjectprotein familyen
dc.subjectprotein foldingen
dc.subjectprotein purificationen
dc.subjectprotein structureen
dc.subjectSCAN domainen
dc.subjectAmino Acid Sequenceen
dc.subjectAnimalsen
dc.subjectCrystallography, X-Rayen
dc.subjectDimerizationen
dc.subjectEmbryonic Stem Cellsen
dc.subjectMiceen
dc.subjectModels, Molecularen
dc.subjectMolecular Sequence Dataen
dc.subjectProtein Structure, Secondaryen
dc.subjectProtein Structure, Tertiaryen
dc.subjectSequence Alignmenten
dc.subjectTranscription Factorsen
dc.titleStructural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206en
dc.typeArticleen
dc.contributor.departmentBiosciences Core Laben
dc.identifier.journalNucleic Acids Researchen
dc.identifier.pmcidPMC3458555en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionLaboratory for Structural Biochemistry, Genome Institute of Singapore, Genome, 60 Biopolis Street, Singapore 138672, Singaporeen
dc.contributor.institutionStem Cell and Developmental Biology, Genome Institute of Singapore, Genome, 60 Biopolis Street, Singapore 138672, Singaporeen
dc.contributor.institutionDepartment of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singaporeen
dc.contributor.institutionNUS Graduate School for Integrative Sciences and Engineering (NGS), Centre for Life Sciences (CeLS), #05-01, 28 Medical Drive, Singapore 117456, Singaporeen
dc.contributor.institutionMedicinal Chemistry Department, H073 Health Science Building, Seattle, WA 98195, United Statesen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorGanesan, Pugalenthien

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