2f9j

From Proteopedia

3.0 angstrom resolution structure of a Y22M mutant of the spliceosomal protein p14 bound to a region of SF3b155

Structural highlights

2f9j is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SF3B6_HUMAN Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex (PubMed:27720643). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA (PubMed:12234937). Directly contacts the pre-mRNA branch site adenosine for the first catalytic step of splicing (PubMed:16432215). Enters the spliceosome and associates with the pre-mRNA branch site as part of the 17S U2 or, in the case of the minor spliceosome, as part of the 18S U11/U12 snRNP complex, and thus may facilitate the interaction of these snRNP with the branch sites of U2 and U12 respectively (PubMed:16432215).^[1] ^[2] ^[3]

Evolutionary Conservation

Checkto colour the structure by Evolutionary Conservation, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The precise excision of introns from precursor mRNAs (pre-mRNAs) in eukaryotes is accomplished by the spliceosome, a complex assembly containing five small nuclear ribonucleoprotein (snRNP) particles. Human p14, a component of the spliceosomal U2 and U11/U12 snRNPs, has been shown to associate directly with the pre-mRNA branch adenosine early in spliceosome assembly and within the fully assembled spliceosome. Here we report the 2.5-A crystal structure of a complex containing p14 and a peptide derived from the p14-associated U2 snRNP component SF3b155. p14 contains an RNA recognition motif (RRM), the surface of which is largely occluded by a C-terminal alpha-helix and a portion of the SF3b155 peptide. An analysis of RNA.protein crosslinking to wild-type and mutant p14 shows that the branch adenosine directly interacts with a conserved aromatic within a pocket on the surface of the complex. This result, combined with a comparison of the structure with known RRMs and pseudoRRMs as well as model-building by using the electron cryomicroscopy structure of a spliceosomal U11/U12 di-snRNP, suggests that p14.SF3b155 presents a noncanonical surface for RNA recognition at the heart of the mammalian spliceosome.

Crystal structure of a core spliceosomal protein interface.,Schellenberg MJ, Edwards RA, Ritchie DB, Kent OA, Golas MM, Stark H, Luhrmann R, Glover JN, MacMillan AM Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1266-71. Epub 2006 Jan 23. PMID:16432215^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..

Citations

reviews cite this structure

-1 more

References

↑ Will CL, Urlaub H, Achsel T, Gentzel M, Wilm M, Luhrmann R. Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p homologue and an SF3b DEAD-box protein. EMBO J. 2002 Sep 16;21(18):4978-88. PMID:12234937
↑ Schellenberg MJ, Edwards RA, Ritchie DB, Kent OA, Golas MM, Stark H, Luhrmann R, Glover JN, MacMillan AM. Crystal structure of a core spliceosomal protein interface. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1266-71. Epub 2006 Jan 23. PMID:16432215
↑ Cretu C, Schmitzova J, Ponce-Salvatierra A, Dybkov O, De Laurentiis EI, Sharma K, Will CL, Urlaub H, Luhrmann R, Pena V. Molecular Architecture of SF3b and Structural Consequences of Its Cancer-Related Mutations. Mol Cell. 2016 Oct 20;64(2):307-319. doi: 10.1016/j.molcel.2016.08.036. Epub 2016, Oct 6. PMID:27720643 doi:http://dx.doi.org/10.1016/j.molcel.2016.08.036
↑ Schellenberg MJ, Edwards RA, Ritchie DB, Kent OA, Golas MM, Stark H, Luhrmann R, Glover JN, MacMillan AM. Crystal structure of a core spliceosomal protein interface. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1266-71. Epub 2006 Jan 23. PMID:16432215