title: 3D structure analysis of PAKs: A clue to the rational design for affinity reagents and blockers.
abstract: The p21-activated kinase (PAK) family plays a versatile role in cell signaling by forming a hub of interactions. PAKs bind the GTPases like RAC and CDC42. Their proline-rich motifs bind SH3 adaptor proteins such as PIX and NCK. PAKs display nuclear localization signal sites and a potential Integrin binding site. No fully complete structure of the PAKs has been published; partial 3D structures of the PAK family kinases include portions of the auto-inhibited PAK1, GTPase bound to small peptides from PAKs, and the kinase domains from PAK1 and PAK4-6 (with small ligands in a few cases). This review focuses on exploring the intermolecular interaction regions in these 3D structures and we offer insights on the missing regions in crystal structure of the auto-inhibited PAK1. Understanding and modulation of PAK intermolecular interactions can pave the way for PAK blockers and biosensors.
authors.affiliation: Bioscience Division; Los Alamos National Laboratory; Los Alamos, NM USA.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Jha
authors.forename: Charlie E M
authors.initials: CE
authors.lastname: Strauss