4OZ1

Crystal structure of human CAPERalpha UHM bound to SF3b155 ULM5

Summary for 4OZ1

• Entry DOI: 10.2210/pdb4oz1/pdb
• Descriptor: RNA-binding protein 39, Splicing factor 3B subunit 1, POTASSIUM ION, ... (6 entities in total)
• Functional Keywords: u2af homology motif, uhm, protein-peptide complex, pre-mrna splicing factor, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 26848.88

Authors

Loerch, S.,Kielkopf, C.L. (deposition date: 2014-02-13, release date: 2014-05-14, Last modification date: 2023-12-27)

Primary citation

Loerch, S.,Maucuer, A.,Manceau, V.,Green, M.R.,Kielkopf, C.L.
Cancer-relevant splicing factor CAPER alpha engages the essential splicing factor SF3b155 in a specific ternary complex.
J.Biol.Chem., 289:17325-17337, 2014

PubMed Abstract: U2AF homology motifs (UHMs) mediate protein-protein interactions with U2AF ligand motifs (ULMs) of pre-mRNA splicing factors. The UHM-containing alternative splicing factor CAPERα regulates splicing of tumor-promoting VEGF isoforms, yet the molecular target of the CAPERα UHM is unknown. Here we present structures of the CAPERα UHM bound to a representative SF3b155 ULM at 1.7 Å resolution and, for comparison, in the absence of ligand at 2.2 Å resolution. The prototypical UHM/ULM interactions authenticate CAPERα as a bona fide member of the UHM family of proteins. We identify SF3b155 as the relevant ULM-containing partner of full-length CAPERα in human cell extracts. Isothermal titration calorimetry comparisons of the purified CAPERα UHM binding known ULM-containing proteins demonstrate that high affinity interactions depend on the presence of an intact, intrinsically unstructured SF3b155 domain containing seven ULM-like motifs. The interplay among bound CAPERα molecules gives rise to the appearance of two high affinity sites in the SF3b155 ULM-containing domain. In conjunction with the previously identified, UHM/ULM-mediated complexes of U2AF(65) and SPF45 with SF3b155, this work demonstrates the capacity of SF3b155 to offer a platform for coordinated recruitment of UHM-containing splicing factors.

PubMed: 24795046
DOI: 10.1074/jbc.M114.558825

Experimental method

X-RAY DIFFRACTION (1.74 Å)