Molecular insights into the membrane-associated phosphatidylinositol 4-kinase IIα

Qiangjun Zhou, Jiangmei Li, Hang Yu, Yujia Zhai, Zhen Gao, Yanxin Liu, Xiaoyun Pang, Lunfeng Zhang, Klaus Schulten (), Fei Sun () and Chang Chen ()
Additional contact information
Qiangjun Zhou: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Jiangmei Li: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Hang Yu: Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign
Yujia Zhai: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Zhen Gao: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Yanxin Liu: University of Illinois at Urbana-Champaign
Xiaoyun Pang: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Lunfeng Zhang: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Klaus Schulten: Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign
Fei Sun: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Chang Chen: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract Phosphatidylinositol 4-kinase IIα (PI4KIIα), a membrane-associated PI kinase, plays a central role in cell signalling and trafficking. Its kinase activity critically depends on palmitoylation of its cysteine-rich motif (-CCPCC-) and is modulated by the membrane environment. Lack of atomic structure impairs our understanding of the mechanism regulating kinase activity. Here we present the crystal structure of human PI4KIIα in ADP-bound form. The structure identifies the nucleotide-binding pocket that differs notably from that found in PI3Ks. Two structural insertions, a palmitoylation insertion and an RK-rich insertion, endow PI4KIIα with the ‘integral’ membrane-binding feature. Molecular dynamics simulations, biochemical and mutagenesis studies reveal that the palmitoylation insertion, containing an amphipathic helix, contributes to the PI-binding pocket and anchors PI4KIIα to the membrane, suggesting that fluctuation of the palmitoylation insertion affects PI4KIIα’s activity. We conclude from our results that PI4KIIα’s activity is regulated indirectly through changes in the membrane environment.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms4552 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4552

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms4552

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().