Structure of phosphorylated SF1 bound to U2AF?? in an essential splicing factor complex.

ABSTRACT: The essential splicing factors U2AF?? 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?? and the pre-mRNA. Here, we reveal that phosphorylation induces essential conformational changes in SF1 and in the SF1/U2AF??/3' splice site complex. Crystal structures of the phosphorylated (P)SF1 domain bound to the C-terminal domain of U2AF?? at 2.29 Å resolution and of the unphosphorylated SF1 domain at 2.48 Å resolution demonstrate that phosphorylation induces a disorder-to-order transition within a previously unknown SF1/U2AF?? 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??/3' splice site assembly. We further determine that SPSP phosphorylation and the SF1/U2AF?? interface are essential in vivo. These results offer a structural prototype for phosphorylation-dependent control of pre-mRNA splicing factors.

SUBMITTER: Wang W 

PROVIDER: S-EPMC3570649 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature