5IFE

Crystal structure of the human SF3b core complex

Summary for 5IFE

• Entry DOI: 10.2210/pdb5ife/pdb
• Descriptor: Splicing factor 3B subunit 5, Splicing factor 3B subunit 1, PHD finger-like domain-containing protein 5A, ... (6 entities in total)
• Functional Keywords: pre-mrna splicing, u2 snrnp, essential splicing factor, splicing
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 307509.16

Authors

Cretu, C.,Dybkov, O.,De Laurentiis, E.,Will, C.L.,Luhrmann, R.,Pena, V. (deposition date: 2016-02-25, release date: 2016-10-26, Last modification date: 2024-05-08)

Primary citation

Cretu, C.,Schmitzova, J.,Ponce-Salvatierra, A.,Dybkov, O.,De Laurentiis, E.I.,Sharma, K.,Will, C.L.,Urlaub, H.,Luhrmann, R.,Pena, V.
Molecular Architecture of SF3b and Structural Consequences of Its Cancer-Related Mutations.
Mol.Cell, 64:307-319, 2016

PubMed Abstract: SF3b is a heptameric protein complex of the U2 small nuclear ribonucleoprotein (snRNP) that is essential for pre-mRNA splicing. Mutations in the largest SF3b subunit, SF3B1/SF3b155, are linked to cancer and lead to alternative branch site (BS) selection. Here we report the crystal structure of a human SF3b core complex, revealing how the distinctive conformation of SF3b155's HEAT domain is maintained by multiple contacts with SF3b130, SF3b10, and SF3b14b. Protein-protein crosslinking enabled the localization of the BS-binding proteins p14 and U2AF65 within SF3b155's HEAT-repeat superhelix, which together with SF3b14b forms a composite RNA-binding platform. SF3b155 residues, the mutation of which leads to cancer, contribute to the tertiary structure of the HEAT superhelix and its surface properties in the proximity of p14 and U2AF65. The molecular architecture of SF3b reveals the spatial organization of cancer-related SF3b155 mutations and advances our understanding of their effects on SF3b structure and function.

PubMed: 27720643
DOI: 10.1016/j.molcel.2016.08.036

Experimental method

X-RAY DIFFRACTION (3.1 Å)