title: Structural organization of a Sex-comb-on-midleg/polyhomeotic copolymer.
abstract: The polycomb group proteins are required for the stable maintenance of gene repression patterns established during development. They function as part of large multiprotein complexes created via a multitude of protein-protein interaction domains. Here we examine the interaction between the SAM domains of the polycomb group proteins polyhomeotic (Ph) and Sex-comb-on-midleg (Scm). Previously we showed that Ph-SAM polymerizes as a helical structure. We find that Scm-SAM also polymerizes, and a crystal structure reveals an architecture similar to the Ph-SAM polymer. These results suggest that Ph-SAM and Scm-SAM form a copolymer. Binding affinity measurements between Scm-SAM and Ph-SAM subunits in different orientations indicate a preference for the formation of a single junction copolymer. To provide a model of the copolymer, we determined the structure of the Ph-SAM/Scm-SAM junction. Similar binding modes are observed in both homo- and heterocomplex formation with minimal change in helix axis direction at the polymer joint. The copolymer model suggests that polymeric Scm complexes could extend beyond the local domains of polymeric Ph complexes on chromatin, possibly playing a role in long range repression.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: Chongwoo A
authors.initials: CA
authors.lastname: Kim
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sawaya
authors.forename: Duilio
authors.initials: D
authors.lastname: Cascio
authors.forename: Woojae
authors.initials: W
authors.lastname: Kim
authors.forename: James U
authors.initials: JU
authors.lastname: Bowie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000737:chemistry; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics*; D004331:Drosophila melanogaster; D005982:Glutathione Transferase / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D009698:Nucleoproteins / Q000737:chemistry / Q000235:genetics*; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D013997:Time Factors
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D009698:Nucleoproteins; D063146:Polycomb-Group Proteins; D011108:Polymers; D012097:Repressor Proteins; C099357:SCM protein, Drosophila; C072820:ph-d protein, Drosophila; D063150:Polycomb Repressive Complex 1; D005982:Glutathione Transferase