9RFB
Crystal Structure of Human Rac1 in Complex with the Scaffold Protein POSH (residues 321-348)
Summary for 9RFB
| Entry DOI | 10.2210/pdb9rfb/pdb |
| Descriptor | Ras-related C3 botulinum toxin substrate 1, E3 ubiquitin-protein ligase SH3RF1, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (7 entities in total) |
| Functional Keywords | gtpase gtp/gdp-binding nucleotide binding, hydrolase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 47457.59 |
| Authors | Kjaer, L.F.,Ielasi, F.S.,Palencia, A.,Jensen, M.R. (deposition date: 2025-06-04, release date: 2025-12-03, Last modification date: 2026-01-07) |
| Primary citation | 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 Cited by 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: 41309611DOI: 10.1038/s41467-025-66420-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.854 Å) |
Structure validation
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