title: Multiple polymer architectures of human polyhomeotic homolog 3 sterile alpha motif.
abstract: 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.
authors.affiliation: Department of Biochemistry, The University of Texas Health Science Center San Antonio, MSC 7760, 7703 Floyd Curl Dr., San Antonio, Texas, 78229.
authors.forename: David R
authors.initials: DR
authors.lastname: Nanyes
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Junco
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Taylor
authors.forename: Angela K
authors.initials: AK
authors.lastname: Robinson
authors.forename: Nicolle L
authors.initials: NL
authors.lastname: Patterson
authors.forename: Ambika
authors.initials: A
authors.lastname: Shivarajpur
authors.forename: Jonathan
authors.initials: J
authors.lastname: Halloran
authors.forename: Seth M
authors.initials: SM
authors.lastname: Hale
authors.forename: Yogeet
authors.initials: Y
authors.lastname: Kaur
authors.forename: P John
authors.initials: PJ
authors.lastname: Hart
authors.forename: Chongwoo A
authors.initials: CA
authors.lastname: Kim
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry; D030562:Databases, Protein; D029721:Drosophila Proteins / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D058105:Polymerization; D011487:Protein Conformation; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050505:Mutant Proteins; C519295:PHC3 protein, human; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C072820:ph-d protein, Drosophila; D063150:Polycomb Repressive Complex 1
keywords: Polycomb group; Polyhomeotic; SAM; chromatin; polymer