Article

Structural insights into the autoactivation mechanism of p21-activated protein kinase.

MOE Key Laboratory for Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Structure (impact factor: 6.35). 12/2011; 19(12):1752-61. DOI:10.1016/j.str.2011.10.013 pp.1752-61
Source: PubMed

ABSTRACT p21-activated kinases (PAKs) play an important role in diverse cellular processes. Full activation of PAKs requires autophosphorylation of a critical threonine/serine located in the activation loop of the kinase domain. Here we report crystal structures of the phosphorylated and unphosphorylated PAK1 kinase domain. The phosphorylated PAK1 kinase domain has a conformation typical of all active protein kinases. Interestingly, the structure of the unphosphorylated PAK1 kinase domain reveals an unusual dimeric arrangement expected in an authentic enzyme-substrate complex, in which the activation loop of the putative "substrate" is projected into the active site of the "enzyme." The enzyme is bound to AMP-PNP and has an active conformation, whereas the substrate is empty and adopts an inactive conformation. Thus, the structure of the asymmetric homodimer mimics a trans-autophosphorylation complex, and suggests that unphosphorylated PAK1 could dynamically adopt both the active and inactive conformations in solution.

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    Article: Mutations in FLS2 Ser-938 Dissect Signaling Activation in FLS2-Mediated Arabidopsis Immunity.
    Yangrong Cao, David J Aceti, Grzegorz Sabat, Junqi Song, Shin-Ichi Makino, Brian G Fox, Andrew F Bent
    [show abstract] [hide abstract]
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    PLoS Pathogens 04/2013; 9(4):e1003313. · 9.13 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

activation loop
 
active conformation
 
active protein kinases
 
active site
 
asymmetric homodimer
 
authentic enzyme-substrate complex
 
conformation typical
 
critical threonine/serine
 
diverse cellular processes
 
inactive conformation
 
inactive conformations
 
kinase domain
 
p21-activated kinases
 
phosphorylated
 
phosphorylated PAK1 kinase domain
 
substrate
 
trans-autophosphorylation complex
 
unphosphorylated PAK1
 
unphosphorylated PAK1 kinase domain
 
unusual dimeric arrangement
 

Jue Wang