9M41

The crystal structure of full-length PAK2 containing K278R and D368N mutants

Summary for 9M41

• Entry DOI: 10.2210/pdb9m41/pdb
• Descriptor: Serine/threonine-protein kinase PAK 2, PHOSPHATE ION (3 entities in total)
• Functional Keywords: inactive pak2, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 121305.35

Authors

Hu, H.-F.,Luo, Z.P.,Wu, J.-W.,Wang, Z.-X. (deposition date: 2025-03-03, release date: 2025-08-13, Last modification date: 2025-10-22)

Primary citation

Hu, H.F.,Luo, Z.,Zhang, Y.,Fang, X.,Zhu, Z.,Wu, J.W.,Wang, Z.X.
Crystal structures of PAK2 reveal new insights into its autoinhibitory mechanism.
Structure, 33:1663-, 2025

PubMed Abstract: Type I p21-activated kinases (PAK1/2/3) exist in an auto-inhibited form and are stimulated by small G-protein binding and auto-phosphorylation. Previous structural and biochemical studies suggested that PAK1 is a dimer in crystals, and probably in a trans-inhibited conformation in solution. Here, we used multiple independent biochemical and biophysical methods to determine the oligomeric state and autoinhibitory mechanism of PAK2. Crystal structures of the full-length and N-terminal truncated PAK2 reveal the molecular basis underlying the PAK2 autoinhibition. Analytical ultracentrifugation studies show that these proteins have molecular weights that are consistent with monomeric species. The solution-phase structure of the full-length PAK2 by small angle X-ray scattering and computational modeling further shows a compact but elongated molecular shape. These results, taken together with the results of previous studies, demonstrate that in contrast with the most widely accepted model, all three type I PAKs are monomeric in solution and auto-inhibited in cis before activation.

PubMed: 40752491
DOI: 10.1016/j.str.2025.07.008

Experimental method

X-RAY DIFFRACTION (3.02 Å)