6N3E

Structure of HIV Tat-specific factor 1 U2AF Homology Motif bound to U2AF ligand motif 4

6N3E の概要

• エントリーDOI: 10.2210/pdb6n3e/pdb
• 分子名称: HIV Tat-specific factor 1, SF3b1 U2AF ligand motif, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: hiv tat-specific factor 1, rna splicing factor, u2af homology motif, uhm, rna binding protein, u2af ligand motif, ulm, protein-peptide complex, pre-mrna splicing factor, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 12273.66

構造登録者

Loerch, S.,Jenkins, J.L.,Kielkopf, C.L. (登録日: 2018-11-15, 公開日: 2019-01-02, 最終更新日: 2024-03-13)

主引用文献

Loerch, S.,Leach, J.R.,Horner, S.W.,Maji, D.,Jenkins, J.L.,Pulvino, M.J.,Kielkopf, C.L.
The pre-mRNA splicing and transcription factor Tat-SF1 is a functional partner of the spliceosome SF3b1 subunit via a U2AF homology motif interface.
J. Biol. Chem., 294:2892-2902, 2019

PubMed Abstract: The transcription elongation and pre-mRNA splicing factor Tat-SF1 associates with the U2 small nuclear ribonucleoprotein (snRNP) of the spliceosome. However, the direct binding partner and underlying interactions mediating the Tat-SF1-U2 snRNP association remain unknown. Here, we identified SF3b1 as a Tat-SF1-interacting subunit of the U2 snRNP. Our 1.1 Å resolution crystal structure revealed that Tat-SF1 contains a U2AF homology motif (UHM) protein-protein interaction module. We demonstrated that Tat-SF1 preferentially and directly binds the SF3b1 subunit compared with other U2AF ligand motif (ULM)-containing splicing factors, and further established that SF3b1 association depends on the integrity of the Tat-SF1 UHM. We next compared the Tat-SF1-binding affinities for each of the five known SF3b1 ULMs and then determined the structures of representative high- and low-affinity SF3b1 ULM complexes with the Tat-SF1 UHM at 1.9 Å and 2.1 Å resolutions, respectively. These structures revealed a canonical UHM-ULM interface, comprising a Tat-SF1 binding pocket for a ULM tryptophan (SF3b1 Trp) and electrostatic interactions with a basic ULM tail. Importantly, we found that SF3b1 regulates Tat-SF1 levels and that these two factors influence expression of overlapping representative transcripts, consistent with a functional partnership of Tat-SF1 and SF3b1. Altogether, these results define a new molecular interface of the Tat-SF1-U2 snRNP complex for gene regulation.

PubMed: 30567737
DOI: 10.1074/jbc.RA118.006764

実験手法

X-RAY DIFFRACTION (1.893 Å)