title: Solution NMR structure of the DNA-binding domain from Scml2 (sex comb on midleg-like 2).
abstract: Scml2 is a member of the Polycomb group of proteins involved in epigenetic gene silencing. Human Scml2 is a part of a multisubunit protein complex, PRC1 (Polycomb repressive complex 1), which is responsible for maintenance of gene repression, prevention of chromatin remodeling, preservation of the "stemness" of the cell, and cell differentiation. Although the majority of PRC1 subunits have been recently characterized, the structure of Scml2 and its role in PRC1-mediated gene silencing remain unknown. In this work a conserved protein domain within human Scml2 has been identified, and its structure was determined by solution NMR spectroscopy. This module was named Scm-like embedded domain, or SLED. Evolutionarily, the SLED domain emerges in the first multicellular organisms, consistent with the role of Scml2 in cell differentiation. Furthermore, it is exclusively found within the Scm-like family of proteins, often accompanied by malignant brain tumor domain (MBT) and sterile α motif (SAM) domains. The domain adopts a novel α/β fold with no structural analogues found in the Protein Data Bank (PDB). The ability of the SLED to bind double-stranded DNA was also examined, and the isolated domain was shown to interact with DNA in a sequence-specific manner. Because PRC1 complexes localize to the promoters of a specific subset of developmental genes in vivo, the SLED domain of Scml2 may provide an important link connecting the PRC1 complexes to their target genes.
authors.affiliation: From the Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut, 06032-3305 bezsonova@uchc.edu.
authors.forename: Irina
authors.initials: I
authors.lastname: Bezsonova
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D020868:Gene Silencing; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010802:Phylogeny; D063146:Polycomb-Group Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C116662:PRC1 protein, human; D063146:Polycomb-Group Proteins; C119751:SCML2 protein, human
keywords: DNA-binding Protein; Epigenetics; NMR; Polycomb; Protein Structure
references.citation: Nucleic Acids Res. 2009 Jun;37(10):3143-52
references.pmid: 19304745
references.citation: Bioinformatics. 2007 Nov 1;23(21):2947-8
references.pmid: 17846036
references.citation: J Mol Biol. 2008 Oct 24;382(5):1107-12
references.pmid: 18706910
references.citation: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W197-201
references.pmid: 18463136
references.citation: Structure. 2003 Jul;11(7):775-89
references.pmid: 12842041
references.citation: Genetics. 1998 Oct;150(2):675-86
references.pmid: 9755199
references.citation: Trends Biochem Sci. 1995 Nov;20(11):478-80
references.pmid: 8578593
references.citation: Magn Reson Chem. 2006 Jul;44 Spec No:S152-7
references.pmid: 16602075
references.citation: Nucleic Acids Res. 2009 Apr;37(7):2204-10
references.pmid: 19233876
references.citation: Mol Cell Biol. 2010 Jun;30(11):2581-3
references.pmid: 20351178
references.citation: Mol Cell Biol. 2010 Jun;30(11):2584-93
references.pmid: 20351181
references.citation: EMBO Rep. 2007 Nov;8(11):1031-7
references.pmid: 17932512
references.citation: Proc Natl Acad Sci U S A. 1998 May 26;95(11):5857-64
references.pmid: 9600884
references.citation: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W545-9
references.pmid: 20457744
references.citation: Nat Protoc. 2007;2(11):2728-33
references.pmid: 18007608
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D302-5
references.pmid: 22053084
references.citation: J Mol Biol. 2012 Nov 9;423(5):702-18
references.pmid: 22954662
references.citation: Development. 2007 Jan;134(2):223-32
references.pmid: 17185323
references.citation: EMBO J. 2009 Jul 8;28(13):1965-77
references.pmid: 19494831
references.citation: J Biomol NMR. 2009 Aug;44(4):213-23
references.pmid: 19548092
references.citation: Genomics. 1999 May 15;58(1):65-72
references.pmid: 10331946
references.citation: Mol Cell. 2012 Feb 10;45(3):344-56
references.pmid: 22325352
references.citation: Dev Genet. 1998;22(1):74-84
references.pmid: 9499582
references.citation: Nat Struct Biol. 2002 Nov;9(11):839-43
references.pmid: 12379844
references.citation: Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
references.pmid: 9757107
references.citation: Mol Cell. 2007 Nov 30;28(4):677-91
references.pmid: 18042461
references.citation: Nat Struct Mol Biol. 2007 Dec;14(12):1229-30
references.pmid: 18026117
references.citation: Mol Cell. 2013 Mar 7;49(5):808-24
references.pmid: 23473600
references.citation: Curr Protoc Bioinformatics. 2006 Jul;Chapter 5:Unit 5.5
references.pmid: 18428766
references.citation: Development. 2009 Nov;136(21):3531-42
references.pmid: 19820181
references.citation: J Biol Chem. 2005 Jul 29;280(30):27769-75
references.pmid: 15905166
references.citation: Development. 2013 Jun;140(12):2525-34
references.pmid: 23715546
references.citation: Cell. 1999 Jul 9;98(1):37-46
references.pmid: 10412979
references.citation: Nucleic Acids Res. 2004 Jan 02;32(1):82-92
references.pmid: 14704346
references.citation: J Biomol NMR. 1995 Nov;6(3):277-93
references.pmid: 8520220
references.citation: Trends Biochem Sci. 2003 Feb;28(2):69-74
references.pmid: 12575993
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D229-32
references.pmid: 18978020
references.citation: Curr Opin Cell Biol. 2007 Jun;19(3):290-7
references.pmid: 17481880
references.citation: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W475-8
references.pmid: 21470960
references.citation: Methods Mol Biol. 2004;278:353-78
references.pmid: 15318003
references.citation: Nucleic Acids Res. 1997 Jan 1;25(1):231-4
references.pmid: 9016542