4fxx

Structure of SF1 coiled-coil domainStructure of SF1 coiled-coil domain

Structural highlights

4fxx is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1opi, 1k1g, 2g4b, 4fxw
Gene:	SF1, ZFM1, ZNF162 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SF01_HUMAN] Necessary for the ATP-dependent first step of spliceosome assembly. Binds to the intron branch point sequence (BPS) 5'-UACUAAC-3' of the pre-mRNA. May act as transcription repressor.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The 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

↑ Arning S, Gruter P, Bilbe G, Kramer A. Mammalian splicing factor SF1 is encoded by variant cDNAs and binds to RNA. RNA. 1996 Aug;2(8):794-810. PMID:8752089
↑ Wang X, Bruderer S, Rafi Z, Xue J, Milburn PJ, Kramer A, Robinson PJ. Phosphorylation of splicing factor SF1 on Ser20 by cGMP-dependent protein kinase regulates spliceosome assembly. EMBO J. 1999 Aug 16;18(16):4549-59. PMID:10449420 doi:http://dx.doi.org/10.1093/emboj/18.16.4549
↑ Zhang D, Paley AJ, Childs G. The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription. J Biol Chem. 1998 Jul 17;273(29):18086-91. PMID:9660765
↑ Wang W, Maucuer A, Gupta A, Manceau V, Thickman KR, Bauer WJ, Kennedy SD, Wedekind JE, Green MR, Kielkopf CL. Structure of Phosphorylated SF1 Bound to U2AF(65) in an Essential Splicing Factor Complex. Structure. 2012 Dec 22. pii: S0969-2126(12)00455-8. doi:, 10.1016/j.str.2012.10.020. PMID:23273425 doi:http://dx.doi.org/10.1016/j.str.2012.10.020

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OCA

[1] Arning S, Gruter P, Bilbe G, Kramer A. Mammalian splicing factor SF1 is encoded by variant cDNAs and binds to RNA. RNA. 1996 Aug;2(8):794-810. PMID:8752089

[2] Wang X, Bruderer S, Rafi Z, Xue J, Milburn PJ, Kramer A, Robinson PJ. Phosphorylation of splicing factor SF1 on Ser20 by cGMP-dependent protein kinase regulates spliceosome assembly. EMBO J. 1999 Aug 16;18(16):4549-59. PMID:10449420 doi:http://dx.doi.org/10.1093/emboj/18.16.4549

[3] Zhang D, Paley AJ, Childs G. The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription. J Biol Chem. 1998 Jul 17;273(29):18086-91. PMID:9660765

[4] Wang W, Maucuer A, Gupta A, Manceau V, Thickman KR, Bauer WJ, Kennedy SD, Wedekind JE, Green MR, Kielkopf CL. Structure of Phosphorylated SF1 Bound to U2AF(65) in an Essential Splicing Factor Complex. Structure. 2012 Dec 22. pii: S0969-2126(12)00455-8. doi:, 10.1016/j.str.2012.10.020. PMID:23273425 doi:http://dx.doi.org/10.1016/j.str.2012.10.020

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