9RFB

Crystal Structure of Human Rac1 in Complex with the Scaffold Protein POSH (residues 321-348)

9RFB の概要

• エントリーDOI: 10.2210/pdb9rfb/pdb
• 分子名称: Ras-related C3 botulinum toxin substrate 1, E3 ubiquitin-protein ligase SH3RF1, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (7 entities in total)
• 機能のキーワード: gtpase gtp/gdp-binding nucleotide binding, hydrolase
• 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: 47457.59

構造登録者

Kjaer, L.F.,Ielasi, F.S.,Palencia, A.,Jensen, M.R. (登録日: 2025-06-04, 公開日: 2025-12-03, 最終更新日: 2026-01-07)

主引用文献

Kjaer, L.F.,Ielasi, F.S.,Winbolt, T.,Delaforge, E.,Tengo, M.,Bessa, L.M.,Marino Perez, L.,Boeri Erba, E.,Bouvignies, G.,Palencia, A.,Jensen, M.R.
Hierarchical folding-upon-binding of an intrinsically disordered protein.
Nat Commun, 16:11346-11346, 2025

PubMed Abstract: Intrinsically disordered proteins (IDPs) often undergo folding-upon-binding to their partners via short linear motifs, typically 5-15 amino acids in length. However, a significant proportion of IDPs do not adhere to this paradigm but fold upon binding through extended regions comprising multiple molecular recognition elements. For these IDPs, the binding mechanisms and the structural characteristics of their folding intermediates remain poorly understood. Here we unveil hierarchical folding of an IDP as it binds to its partner, exemplified by the disordered signaling effector POSH and the small GTPase Rac1. By combining nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, we resolve at atomic resolution how POSH transitions from a fully disordered state to a highly ordered, Rac1-bound conformation through two structurally distinct folding intermediates. The folding of each element is contingent on the successful structuring of the preceding element, highlighting a hierarchical folding-upon-binding mechanism. Our work highlights the potential of targeting folding intermediates and conformational transitions to unlock therapeutic opportunities for IDPs.

PubMed: 41309611
DOI: 10.1038/s41467-025-66420-5

実験手法

X-RAY DIFFRACTION (1.854 Å)