4OZ0

Crystal structure of human CAPERalpha U2AF homology motif (apo-state)

4OZ0 の概要

• エントリーDOI: 10.2210/pdb4oz0/pdb
• 分子名称: RNA-binding protein 39, CHLORIDE ION (3 entities in total)
• 機能のキーワード: u2af homology motif, uhm, protein-peptide complex, pre-mrna splicing factor, transcription
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25356.12

構造登録者

Loerch, S.,Kielkopf, C.L. (登録日: 2014-02-13, 公開日: 2014-05-14, 最終更新日: 2023-09-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)