4FXW

Structure of phosphorylated SF1 complex with U2AF65-UHM domain

Summary for 4FXW

• Entry DOI: 10.2210/pdb4fxw/pdb
• Related: 1K1G 1OPI 2G4B 4FXX
• Descriptor: Splicing factor U2AF 65 kDa subunit, Splicing factor 1, SULFATE ION, ... (4 entities in total)
• Functional Keywords: uhm, pre-mrna splicing factor, protein binding, phosphorylation
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P26368 Q15637
• Total number of polymer chains: 4
• Total formula weight: 54041.04

Authors

Wang, W.,Bauer, W.J.,Wedekind, J.E.,Kielkopf, C.L. (deposition date: 2012-07-03, release date: 2013-01-16, Last modification date: 2017-11-15)

Primary citation

Wang, W.,Maucuer, A.,Gupta, A.,Manceau, V.,Thickman, K.R.,Bauer, W.J.,Kennedy, S.D.,Wedekind, J.E.,Green, M.R.,Kielkopf, C.L.
Structure of Phosphorylated SF1 Bound to U2AF(65) in an Essential Splicing Factor Complex.
Structure, 21:197-208, 2013

PubMed Abstract: The essential splicing factors U2AF⁶⁵ 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 U2AF⁶⁵ and the pre-mRNA. Here, we reveal that phosphorylation induces essential conformational changes in SF1 and in the SF1/U2AF⁶⁵/3' splice site complex. Crystal structures of the phosphorylated (P)SF1 domain bound to the C-terminal domain of U2AF⁶⁵ 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/U2AF⁶⁵ 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/U2AF⁶⁵/3' splice site assembly. We further determine that SPSP phosphorylation and the SF1/U2AF⁶⁵ interface are essential in vivo. These results offer a structural prototype for phosphorylation-dependent control of pre-mRNA splicing factors.

PubMed: 23273425
DOI: 10.1016/j.str.2012.10.020

Experimental method

X-RAY DIFFRACTION (2.29 Å)