7ZY4

Crystal structure of human CstF77 in complex with hFip1

7ZY4 の概要

• エントリーDOI: 10.2210/pdb7zy4/pdb
• 分子名称: Cleavage stimulation factor subunit 3, hFip1, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: complex, 3' end processing, cstf, cpsf, gene regulation
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 82108.86

構造登録者

Muckenfuss, L.M.,Jinek, M. (登録日: 2022-05-23, 公開日: 2022-09-14, 最終更新日: 2024-01-31)

主引用文献

Muckenfuss, L.M.,Migenda Herranz, A.C.,Boneberg, F.M.,Clerici, M.,Jinek, M.
Fip1 is a multivalent interaction scaffold for processing factors in human mRNA 3' end biogenesis.
Elife, 11:-, 2022

PubMed Abstract: 3' end formation of most eukaryotic mRNAs is dependent on the assembly of a ~1.5 MDa multiprotein complex, that catalyzes the coupled reaction of pre-mRNA cleavage and polyadenylation. In mammals, the cleavage and polyadenylation specificity factor (CPSF) constitutes the core of the 3' end processing machinery onto which the remaining factors, including cleavage stimulation factor (CstF) and poly(A) polymerase (PAP), assemble. These interactions are mediated by Fip1, a CPSF subunit characterized by high degree of intrinsic disorder. Here, we report two crystal structures revealing the interactions of human Fip1 (hFip1) with CPSF30 and CstF77. We demonstrate that CPSF contains two copies of hFip1, each binding to the zinc finger (ZF) domains 4 and 5 of CPSF30. Using polyadenylation assays we show that the two hFip1 copies are functionally redundant in recruiting one copy of PAP, thereby increasing the processivity of RNA polyadenylation. We further show that the interaction between hFip1 and CstF77 is mediated via a short motif in the N-terminal 'acidic' region of hFip1. In turn, CstF77 competitively inhibits CPSF-dependent PAP recruitment and 3' polyadenylation. Taken together, these results provide a structural basis for the multivalent scaffolding and regulatory functions of hFip1 in 3' end processing.

PubMed: 36073787
DOI: 10.7554/eLife.80332

実験手法

X-RAY DIFFRACTION (2.55 Å)