STK40 Is a Pseudokinase that Binds the E3 Ubiquitin Ligase COP1
Abstract
Serine/threonine kinase 40 (STK40) was originally identified as a distant homolog of Tribbles-family proteins. Despite accumulating data attesting to the importance of STK40 in a variety of different physiologic processes, little is known about its biological activity or mechanism of action.In this work, we show that STK40 interacts with Constitutive Photomorphogenic Protein 1 (COP1), relying primarily on a C-terminal sequence analogous to the motif found in Tribbles proteins. In order to further elucidate structure-function relationships in STK40, we determined the crystal structure of the STK40 kinase homology domain at 2.5 Å resolution. The structure, together with ATP-binding assay results, show that STK40 is a pseudokinase, in which substitutions of conserved residues within the kinase domain prevent ATP binding. Although the structure of the kinase homology domain diverges from the analogous region of Trib1, the results reported here suggest functional parallels between STK40 and Tribbles-family proteins as COP1 adaptors.
- Authors:
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH)
- OSTI Identifier:
- 1419805
- Alternate Identifier(s):
- OSTI ID: 1416246; OSTI ID: 1430311
- Grant/Contract Number:
- AC02-06CH11357; R01 CA092433; P50 GM107618; K08 CA166227; P41 GM103403; S10 RR029205
- Resource Type:
- Published Article
- Journal Name:
- Structure
- Additional Journal Information:
- Journal Name: Structure Journal Volume: 25 Journal Issue: 2; Journal ID: ISSN 0969-2126
- Publisher:
- Elsevier
- Country of Publication:
- United Kingdom
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; pseudokinase; COP1E3 ligase; X-ray crystallography; ATP binding; STK40; RFWD2; SgK495; Tribbles; SINK-homologous kinase
Citation Formats
Durzynska, Izabela, Xu, Xiang, Adelmant, Guillaume, Ficarro, Scott B., Marto, Jarrod A., Sliz, Piotrek, Uljon, Sacha, and Blacklow, Stephen C. STK40 Is a Pseudokinase that Binds the E3 Ubiquitin Ligase COP1. United Kingdom: N. p., 2017.
Web. doi:10.1016/j.str.2016.12.008.
Durzynska, Izabela, Xu, Xiang, Adelmant, Guillaume, Ficarro, Scott B., Marto, Jarrod A., Sliz, Piotrek, Uljon, Sacha, & Blacklow, Stephen C. STK40 Is a Pseudokinase that Binds the E3 Ubiquitin Ligase COP1. United Kingdom. https://doi.org/10.1016/j.str.2016.12.008
Durzynska, Izabela, Xu, Xiang, Adelmant, Guillaume, Ficarro, Scott B., Marto, Jarrod A., Sliz, Piotrek, Uljon, Sacha, and Blacklow, Stephen C. Thu .
"STK40 Is a Pseudokinase that Binds the E3 Ubiquitin Ligase COP1". United Kingdom. https://doi.org/10.1016/j.str.2016.12.008.
@article{osti_1419805,
title = {STK40 Is a Pseudokinase that Binds the E3 Ubiquitin Ligase COP1},
author = {Durzynska, Izabela and Xu, Xiang and Adelmant, Guillaume and Ficarro, Scott B. and Marto, Jarrod A. and Sliz, Piotrek and Uljon, Sacha and Blacklow, Stephen C.},
abstractNote = {Serine/threonine kinase 40 (STK40) was originally identified as a distant homolog of Tribbles-family proteins. Despite accumulating data attesting to the importance of STK40 in a variety of different physiologic processes, little is known about its biological activity or mechanism of action.In this work, we show that STK40 interacts with Constitutive Photomorphogenic Protein 1 (COP1), relying primarily on a C-terminal sequence analogous to the motif found in Tribbles proteins. In order to further elucidate structure-function relationships in STK40, we determined the crystal structure of the STK40 kinase homology domain at 2.5 Å resolution. The structure, together with ATP-binding assay results, show that STK40 is a pseudokinase, in which substitutions of conserved residues within the kinase domain prevent ATP binding. Although the structure of the kinase homology domain diverges from the analogous region of Trib1, the results reported here suggest functional parallels between STK40 and Tribbles-family proteins as COP1 adaptors.},
doi = {10.1016/j.str.2016.12.008},
journal = {Structure},
number = 2,
volume = 25,
place = {United Kingdom},
year = {Thu Jan 12 00:00:00 EST 2017},
month = {Thu Jan 12 00:00:00 EST 2017}
}
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https://doi.org/10.1016/j.str.2016.12.008
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