4fxw
From Proteopedia
Structure of phosphorylated SF1 complex with U2AF65-UHM domain
Structural highlights
FunctionU2AF2_HUMAN Necessary for the splicing of pre-mRNA. Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10.[1] [2] [3] Publication Abstract from PubMedThe essential splicing factors U2AF(65) and SF1 cooperatively bind consensus sequences at the 3' end of introns. Phosphorylation of SF1 on a highly conserved "SPSP" motif enhances its interaction with U2AF(65) and the pre-mRNA. Here, we reveal that phosphorylation induces essential conformational changes in SF1 and in the SF1/U2AF(65)/3' splice site complex. Crystal structures of the phosphorylated (P)SF1 domain bound to the C-terminal domain of U2AF(65) at 2.29 A resolution and of the unphosphorylated SF1 domain at 2.48 A resolution demonstrate that phosphorylation induces a disorder-to-order transition within a previously unknown SF1/U2AF(65) interface. We find by small-angle X-ray scattering that the local folding of the SPSP motif transduces into global conformational changes in the nearly full-length (P)SF1/U2AF(65)/3' splice site assembly. We further determine that SPSP phosphorylation and the SF1/U2AF(65) interface are essential in vivo. These results offer a structural prototype for phosphorylation-dependent control of pre-mRNA splicing factors. Structure of Phosphorylated SF1 Bound to U2AF(65) in an Essential Splicing Factor Complex.,Wang W, Maucuer A, Gupta A, Manceau V, Thickman KR, Bauer WJ, Kennedy SD, Wedekind JE, Green MR, Kielkopf CL Structure. 2012 Dec 22. pii: S0969-2126(12)00455-8. doi:, 10.1016/j.str.2012.10.020. PMID:23273425[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|