title: Crystal structure of murine CstF-77: dimeric association and implications for polyadenylation of mRNA precursors.
abstract: Cleavage stimulation factor (CstF) is a heterotrimeric protein complex essential for polyadenylation of mRNA precursors. The 77 kDa subunit, CstF-77, is known to mediate interactions with the other two subunits of CstF as well as with other components of the polyadenylation machinery. We report here the crystal structure of the HAT (half a TPR) domain of murine CstF-77, as well as its C-terminal subdomain. Structural and biochemical studies show that the HAT domain consists of two subdomains, HAT-N and HAT-C domains, with drastically different orientations of their helical motifs. The structures reveal a highly elongated dimer, spanning 165 A, with the dimerization mediated by the HAT-C domain. Light-scattering studies, yeast two-hybrid assays, and analytical ultracentrifugation measurements confirm this self-association. The mode of dimerization and the relative arrangement of the HAT-N and HAT-C domains are unique to CstF-77. Our data support a role for CstF dimerization in pre-mRNA 3' end processing.
authors: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors: Yun
authors: Y
authors: Bai
authors: Thierry C
authors: TC
authors: Auperin
authors: Chi-Yuan
authors: CY
authors: Chou
authors: Gu-Gang
authors: GG
authors: Chang
authors: James L
authors: JL
authors: Manley
authors: Liang
authors: L
authors: Tong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D039241:Cleavage Stimulation Factor / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019281:Dimerization; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D026723:Polyadenylation; D011487:Protein Conformation; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D039241:Cleavage Stimulation Factor; C519384:CstF-77 protein, mouse; D012322:RNA Precursors; D012333:RNA, Messenger; D011994:Recombinant Proteins