PDBsum entry 6fd3

Transferase

PDB id: 6fd3

Contents

Protein chain

297 a.a.

Ligands

ADP

EDO ×2

Metals

_MG ×2

Waters ×276

References listed in PDB file

Key reference

• Title: Solution structures and biophysical analysis of full-Length group a paks reveal they are monomeric and auto-Inhibited in cis.
• Authors: F.J.Sorrell, L.M.Kilian, J.M.Elkins.
• Ref.: Biochem J, 2019, 476, 1037-1051. [DOI no: 10.1042/BCJ20180867]
• PubMed id: 30858169

Abstract

The group A p21-activated kinases (PAKs) exist in an auto-inhibited form until activated by GTPase binding and auto-phosphorylation. In the auto-inhibited form, a regulatory domain binds to the kinase domain (KD) blocking the binding of substrates, and CDC42 or Rac binding to the regulatory domain relieves this auto-inhibition allowing auto-phosphorylation on the KD activation loop. We have determined the crystal structure of the PAK3 catalytic domain and by small angle X-ray scattering, the solution-phase structures of full-length inactive PAK1 and PAK3. The structures reveal a compact but elongated molecular shape that demonstrates that, together with multiple independent biophysical measurements and in contrast with previous assumptions, group A PAKs are monomeric both before and after activation, consistent with an activation mechanism of cis-auto-inhibition and initial cis-auto-phosphorylation, followed by transient dimerisation to allow trans-auto-phosphorylation for full activation, yielding a monomeric active PAK protein.