Structure of the Dictyostelium Myosin-II Heavy Chain Kinase A (MHCK-A) α-kinase domain apoenzyme reveals a novel autoinhibited conformation
Abstract
The α-kinases are a family of a typical protein kinases present in organisms ranging from protozoa to mammals. Here we report an autoinhibited conformation for the α-kinase domain of Dictyostelium myosin-II heavy chain kinase A (MHCK-A) in which nucleotide binding to the catalytic cleft, located at the interface between an N-terminal and C-terminal lobe, is sterically blocked by the side chain of a conserved arginine residue (Arg592). Previous α-kinase structures have shown that an invariant catalytic aspartic acid residue (Asp766) is phosphorylated. Unexpectedly, in the autoinhibited conformation the phosphoryl group is transferred to the adjacent Asp663, creating an interaction network that stabilizes the autoinhibited state. The results suggest that Asp766 phosphorylation may play both catalytic and regulatory roles. The autoinhibited structure also provides the first view of a phosphothreonine residue docked into the phospho-specific allosteric binding site (Pi-pocket) in the C-lobe of the α-kinase domain.
- Authors:
-
- Queen's Univ., Kingston, ON (Canada)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- Natural Science and Engineering Research Council of Canada Discovery
- OSTI Identifier:
- 1262431
- Grant/Contract Number:
- RGPIN 391522; RGPIN 203705
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 6; Journal Issue: 1; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Biochemistry; Structural biology
Citation Formats
Ye, Qilu, Yang, Yidai, van Staalduinen, Laura, Crawley, Scott William, Liu, Linda, Brennan, Stephanie, Côté, Graham P., and Jia, Zongchao. Structure of the Dictyostelium Myosin-II Heavy Chain Kinase A (MHCK-A) α-kinase domain apoenzyme reveals a novel autoinhibited conformation. United States: N. p., 2016.
Web. doi:10.1038/srep26634.
Ye, Qilu, Yang, Yidai, van Staalduinen, Laura, Crawley, Scott William, Liu, Linda, Brennan, Stephanie, Côté, Graham P., & Jia, Zongchao. Structure of the Dictyostelium Myosin-II Heavy Chain Kinase A (MHCK-A) α-kinase domain apoenzyme reveals a novel autoinhibited conformation. United States. https://doi.org/10.1038/srep26634
Ye, Qilu, Yang, Yidai, van Staalduinen, Laura, Crawley, Scott William, Liu, Linda, Brennan, Stephanie, Côté, Graham P., and Jia, Zongchao. Mon .
"Structure of the Dictyostelium Myosin-II Heavy Chain Kinase A (MHCK-A) α-kinase domain apoenzyme reveals a novel autoinhibited conformation". United States. https://doi.org/10.1038/srep26634. https://www.osti.gov/servlets/purl/1262431.
@article{osti_1262431,
title = {Structure of the Dictyostelium Myosin-II Heavy Chain Kinase A (MHCK-A) α-kinase domain apoenzyme reveals a novel autoinhibited conformation},
author = {Ye, Qilu and Yang, Yidai and van Staalduinen, Laura and Crawley, Scott William and Liu, Linda and Brennan, Stephanie and Côté, Graham P. and Jia, Zongchao},
abstractNote = {The α-kinases are a family of a typical protein kinases present in organisms ranging from protozoa to mammals. Here we report an autoinhibited conformation for the α-kinase domain of Dictyostelium myosin-II heavy chain kinase A (MHCK-A) in which nucleotide binding to the catalytic cleft, located at the interface between an N-terminal and C-terminal lobe, is sterically blocked by the side chain of a conserved arginine residue (Arg592). Previous α-kinase structures have shown that an invariant catalytic aspartic acid residue (Asp766) is phosphorylated. Unexpectedly, in the autoinhibited conformation the phosphoryl group is transferred to the adjacent Asp663, creating an interaction network that stabilizes the autoinhibited state. The results suggest that Asp766 phosphorylation may play both catalytic and regulatory roles. The autoinhibited structure also provides the first view of a phosphothreonine residue docked into the phospho-specific allosteric binding site (Pi-pocket) in the C-lobe of the α-kinase domain.},
doi = {10.1038/srep26634},
journal = {Scientific Reports},
number = 1,
volume = 6,
place = {United States},
year = {Mon May 23 00:00:00 EDT 2016},
month = {Mon May 23 00:00:00 EDT 2016}
}
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Works referencing / citing this record:
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