Multiple polymer architectures of human polyhomeotic homolog 3 sterile alpha motif
David R. Nanyes
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorSarah E. Junco
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorAlexander B. Taylor
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
X-ray Crystallography Core Laboratory, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorAngela K. Robinson
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorNicolle L. Patterson
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorAmbika Shivarajpur
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorJonathan Halloran
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorSeth M. Hale
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorYogeet Kaur
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorP. John Hart
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
X-ray Crystallography Core Laboratory, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Department of Veterans Affairs, South Texas Veterans Health Care System, San Antonio, Texas, 78229
Search for more papers by this authorCorresponding Author
Chongwoo A. Kim
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Correspondence to: Chongwoo A. Kim, Department of Biochemistry, University of Texas Health Science Center at San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, TX 78229. E-mail: [email protected]Search for more papers by this authorDavid R. Nanyes
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorSarah E. Junco
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorAlexander B. Taylor
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
X-ray Crystallography Core Laboratory, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorAngela K. Robinson
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorNicolle L. Patterson
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorAmbika Shivarajpur
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorJonathan Halloran
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorSeth M. Hale
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorYogeet Kaur
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Search for more papers by this authorP. John Hart
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
X-ray Crystallography Core Laboratory, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Department of Veterans Affairs, South Texas Veterans Health Care System, San Antonio, Texas, 78229
Search for more papers by this authorCorresponding Author
Chongwoo A. Kim
Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229
Correspondence to: Chongwoo A. Kim, Department of Biochemistry, University of Texas Health Science Center at San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, TX 78229. E-mail: [email protected]Search for more papers by this authorABSTRACT
The self-association of sterile alpha motifs (SAMs) into a helical polymer architecture is a critical functional component of many different and diverse array of proteins. For the Drosophila Polycomb group (PcG) protein Polyhomeotic (Ph), its SAM polymerization serves as the structural foundation to cluster multiple PcG complexes, helping to maintain a silenced chromatin state. Ph SAM shares 64% sequence identity with its human ortholog, PHC3 SAM, and both SAMs polymerize. However, in the context of their larger protein regions, PHC3 SAM forms longer polymers compared with Ph SAM. Motivated to establish the precise structural basis for the differences, if any, between Ph and PHC3 SAM, we determined the crystal structure of the PHC3 SAM polymer. PHC3 SAM uses the same SAM–SAM interaction as the Ph SAM sixfold repeat polymer. Yet, PHC3 SAM polymerizes using just five SAMs per turn of the helical polymer rather than the typical six per turn observed for all SAM polymers reported to date. Structural analysis suggested that malleability of the PHC3 SAM would allow formation of not just the fivefold repeat structure but also possibly others. Indeed, a second PHC3 SAM polymer in a different crystal form forms a sixfold repeat polymer. These results suggest that the polymers formed by PHC3 SAM, and likely others, are dynamic. The functional consequence of the variable PHC3 SAM polymers may be to create different chromatin architectures. Proteins 2014; 82:2823–2830. © 2014 Wiley Periodicals, Inc.
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REFERENCES
- 1Qiao F, Bowie JU. The many faces of SAM. Sci STKE 2005; 2005: re7.
- 2Kim CA, Phillips ML, Kim W, Gingery M, Tran HH, Robinson MA, Faham S, Bowie JU. Polymerization of the SAM domain of TEL in leukemogenesis and transcriptional repression. EMBO J 2001; 20: 4173–4182.
- 3Kim CA, Gingery M, Pilpa RM, Bowie JU. The SAM domain of polyhomeotic forms a helical polymer. Nat Struct Biol 2002; 9: 453–457.
- 4Qiao F, Song H, Kim CA, Sawaya MR, Hunter JB, Gingery M, Rebay I, Courey AJ, Bowie JU. Derepression by depolymerisation: structural insights into the regulation of Yan by Mae. Cell 2004; 118: 163–173.
- 5Kim CA, Sawaya MR, Cascio D, Kim W, Bowie JU. Structural organization of a sex-comb-on-midleg/polyhomeotic copolymer. J Biol Chem 2005; 280: 27769–27775.
- 6Baron MK, Boeckers TM, Vaida B, Faham S, Gingery M, Sawaya MR, Salyer D, Gundelfinger ED, Bowie JU. An architectural framework that may lie at the core of the postsynaptic density. Science 2006; 311: 531–535.
- 7Harada BT, Knight MJ, Imai S, Qiao F, Ramachander R, Sawaya MR, Gingery M, Sakane F, Bowie JU. Regulation of enzyme localization by polymerization: polymer formation by the SAM domain of diacylglycerol kinase delta1. Structure 2008; 16: 380–387.
- 8Di Pietro SM, Cascio D, Feliciano D, Bowie JU, Payne GS. Regulation of clathrin adaptor function in endocytosis: novel role for the SAM domain. EMBO J 2010; 29: 1033–1044.
- 9Stafford RL, Hinde E, Knight MJ, Pennella MA, Ear J, Digman MA, Gratton E, Bowie JU. Tandem SAM domain structure of human Caskin1: a presynaptic, self-assembling scaffold for CASK. Structure 2011; 19: 1826–1836.
- 10Classen AK, Bunker BD, Harvey KF, Vaccari T, Bilder D. A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT signaling. Nat Genet 2009; 41: 1150–1155.
- 11Martinez AM, Schuettengruber B, Sakr S, Janic A, Gonzalez C, Cavalli G. Polyhomeotic has a tumor suppressor activity mediated by repression of Notch signaling. Nat Genet 2009; 41: 1076–1082.
- 12Deshpande AM, Akunowicz JD, Reveles XT, Patel BB, Saria EA, Gorlick RG, Naylor SL, Leach RJ, Hansen MF. PHC3, a component of the hPRC-H complex, associates with E2F6 during G(0) and is lost in osteosarcoma tumors. Oncogene 2007; 26: 1714–1722.
- 13Crea F, Sun L, Pikor L, Frumento P, Lam WL, Helgason CD. Mutational analysis of Polycomb genes in solid tumours identifies PHC3 amplification as a possible cancer-driving genetic alteration. Br J Cancer 2013; 109: 1699–1702.
- 14Robinson AK, Leal BZ, Chadwell LV, Wang R, Ilangovan U, Kaur Y, Junco SE, Schirf V, Osmulski PA, Gaczynska M, Hinck AP, Demeler B, McEwen DG, Kim CA. The growth-suppressive function of the polycomb group protein polyhomeotic is mediated by polymerization of its sterile alpha motif (SAM) domain. J Biol Chem 2012; 287: 8702–8713.
- 15Isono K, Endo TA, Ku M, Yamada D, Suzuki R, Sharif J, Ishikura T, Toyoda T, Bernstein BE, Koseki H. SAM domain polymerization links subnuclear clustering of PRC1 to gene silencing. Dev Cell 2013; 26: 565–577.
- 16Robinson AK, Leal BZ, Nanyes DR, Kaur Y, Ilangovan U, Schirf V, Hinck AP, Demeler B, Kim CA. Human polyhomeotic homolog 3 (PHC3) sterile alpha motif (SAM) linker allows open-ended polymerization of PHC3 SAM. Biochemistry 2012; 51: 5379–5386.
- 17Kabsch W. Xds. Acta Crystallogr D Biol Crystallogr 2010; 66: 125–132.
- 18McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ. Phaser crystallographic software. J Appl Crystallogr 2007; 40: 658–674.
- 19Emsley P, Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 2004; 60: 2126–2132.
- 20Adams PD, Grosse-Kunstleve RW, Hung LW, Ioerger TR, McCoy AJ, Moriarty NW, Read RJ, Sacchettini JC, Sauter NK, Terwilliger TC. PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr D Biol Crystallogr 2002; 58: 1948–1954.
- 21Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem 2004; 25: 1605–1612.
- 22Lebedev AA, Isupov MN. Space group validation with Zanuda. CCP4 Newsletter Prot Crystallogr 2012: 53.
- 23Nauli S, Farr S, Lee YJ, Kim HY, Faham S, Bowie JU. Polymer-driven crystallization. Protein Sci 2007; 16: 2542–2551.
- 24Tomotsune D, Takihara Y, Berger J, Duhl D, Joo S, Kyba M, Shirai M, Ohta H, Matsuda Y, Honda BM, Simon J, Shimada K, Brock HW, Randazzo F. A novel member of murine Polycomb-group proteins, Sex comb on midleg homolog protein, is highly conserved, and interacts with RAE28/mph1 in vitro. Differentiation 1999; 65: 229–239.
- 25Peterson AJ, Kyba M, Bornemann D, Morgan K, Brock HW, Simon J. A domain shared by the Polycomb group proteins Scm and ph mediates heterotypic and homotypic interactions. Mol Cell Biol 1997; 17: 6683–6692.
- 26Peterson AJ, Mallin DR, Francis NJ, Ketel CS, Stamm J, Voeller RK, Kingston RE, Simon JA. Requirement for sex comb on midleg protein interactions in Drosophila polycomb group repression. Genetics 2004; 167: 1225–1239.
- 27Isono K, Fujimura Y, Shinga J, Yamaki M, O-Wang J, Takihara Y, Murahashi Y, Takada Y, Mizutani-Koseki Y, Koseki H. Mammalian polyhomeotic homologues phc2 and phc1 act in synergy to mediate polycomb repression of hox genes. Mol Cell Biol 2005; 25: 6694–6706.
- 28Tran HH, Kim CA, Faham S, Siddall MC, Bowie JU. Native interface of the SAM domain polymer of TEL. BMC Struct Biol 2002; 2: 5.
- 29Leettola CN, Knight MJ, Cascio D, Hoffman S, Bowie JU. BMC Struct Biol 2014; 14: 17.
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