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3D structure analysis of PAKs: A clue to the rational design for affinity reagents and blockers

Journal Article · · Cellular Logistics (Online)
DOI:https://doi.org/10.4161/cl.21883· OSTI ID:1629289
 [1];  [2]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); DOE/OSTI
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
+ Show Author Affiliations

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.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; USDOE Laboratory Directed Research and Development (LDRD) Program
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1629289
Journal Information:
Cellular Logistics (Online), Journal Name: Cellular Logistics (Online) Journal Issue: 2 Vol. 2; ISSN 2159-2799
Publisher:
Taylor & FrancisCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (4)

Computational Insight into p21-Activated Kinase 4 Inhibition: A Combined Ligand- and Structure-Based Approach journal March 2014
Targeting PAK1 journal February 2017
Targeting PKCι-PAK1 signaling pathways in EGFR and KRAS mutant adenocarcinoma and lung squamous cell carcinoma journal October 2019
The PAKs come of age: Celebrating 18 years of discovery journal April 2012

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AID
auto-inhibitory domain
ATP
adenosine triphosphate
CFP
cyan fluorescent protein
CRIB
CDC42/RAC interactive binding
Di
dimerization segment
IS
inhibitory switch
Ki
kinase inhibitory
PAK
p21-activated kinase
PDB
Protein Data Bank
RMS
SH2
SH3
src homology region 3
root mean square
src homology region 2