A glutamate switch controls voltage-sensitive phosphatase function.

Nature Structural & Molecular Biology
Lijun LiuDaniel L Minor

Abstract

The Ciona intestinalis voltage-sensing phosphatase (Ci-VSP) couples a voltage-sensing domain (VSD) to a lipid phosphatase that is similar to the tumor suppressor PTEN. How the VSD controls enzyme function has been unclear. Here, we present high-resolution crystal structures of the Ci-VSP enzymatic domain that reveal conformational changes in a crucial loop, termed the 'gating loop', that controls access to the active site by a mechanism in which residue Glu411 directly competes with substrate. Structure-based mutations that restrict gating loop conformation impair catalytic function and demonstrate that Glu411 also contributes to substrate selectivity. Structure-guided mutations further define an interaction between the gating loop and linker that connects the phosphatase to the VSD for voltage control of enzyme activity. Together, the data suggest that functional coupling between the gating loop and the linker forms the heart of the regulatory mechanism that controls voltage-dependent enzyme activation.

References

Jan 17, 1995·Proceedings of the National Academy of Sciences of the United States of America·B K ShoichetB W Matthews
Mar 11, 1994·Science·D BarfordN K Tonks
Nov 1, 1996·Cell·J M DenuJ E Dixon
May 4, 1999·Trends in Cell Biology·T Maehama, J E Dixon
Feb 22, 2000·The Journal of Biological Chemistry·H Yerushalmi, S Schuldiner
Jun 8, 2001·Annual Review of Biochemistry·T MaehamaJ E Dixon
Oct 5, 2001·Molecular and Cellular Biology·J N AndersenN P Møller
Jan 9, 2004·The Biochemical Journal·Steven M WalkerC Peter Downes
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
May 20, 2005·Nature·Yoshimichi MurataYasushi Okamura
Oct 27, 2005·Molecular Interventions·Carolyn A Worby, Jack E Dixon
Dec 18, 2007·Nature Structural & Molecular Biology·Susy C KohoutEhud Y Isacoff
Jan 25, 2008·Nature Reviews. Molecular Cell Biology·Mark A Lemmon
Feb 27, 2008·The FEBS Journal·Lydia TaberneroStefan E Szedlacsek
Mar 21, 2008·Nature Reviews. Molecular Cell Biology·Francisco Bezanilla
Jun 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Hirohide IwasakiYasushi Okamura
Nov 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Daniel G IsomBertrand García-Moreno
Dec 17, 2008·The Journal of Physiology·Yasushi OkamuraHirohide Iwasaki
Dec 31, 2008·Proceedings of the National Academy of Sciences of the United States of America·Meghdad RahdarPeter N Devreotes
Jul 1, 2009·The Journal of General Physiology·Carlos A Villalba-GaleaFrancisco Bezanilla
Apr 7, 2010·Nature Chemical Biology·Susy C KohoutEhud Y Isacoff
Mar 2, 2011·Physiology·Yasushi Okamura, Jack E Dixon
May 28, 2011·Journal of Cellular Physiology·William J RatzanLaurinda A Jaffe
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

❮ Previous
Next ❯

Citations

May 9, 2013·Nature Communications·Stephan A PlessChristopher A Ahern
Oct 16, 2013·The Journal of General Physiology·Carlos A Villalba-GaleaFrancisco Bezanilla
Aug 17, 2012·Journal of Lipid Research·Christian R HalaszovichDominik Oliver
Aug 8, 2013·PloS One·Kirstin HobigerThomas Friedrich
Feb 16, 2016·Nature Chemical Biology·Liang Hong, Francesco Tombola
Feb 16, 2016·Nature Chemical Biology·Sasha S Grimm, Ehud Y Isacoff
Dec 20, 2015·Biophysical Journal·Mario G RosascoSandra M Bajjalieh
Sep 17, 2013·Journal of Cellular Physiology·Shinji YamaguchiKoichi J Homma
Sep 19, 2014·Biochemical Society Transactions·Antreas C Kalli, Mark S P Sansom
Sep 30, 2014·Biochimica Et Biophysica Acta·FoSheng Hsu, Yuxin Mao
Apr 7, 2012·Cellular Signalling·Carlos A Villalba-Galea
May 26, 2016·Proceedings of the National Academy of Sciences of the United States of America·Dongil KeumByung-Chang Suh
Jun 19, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yasushi Okamura
Apr 19, 2018·Journal of Cellular Physiology·Jianping ZhangXuan Zhang
Feb 19, 2013·Angewandte Chemie·Guillaume BortPeter I Dalko
Oct 13, 2018·The Journal of Physiology·Souhei Sakata, Yasushi Okamura
Mar 12, 2019·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Yasushi Okamura, Yoshifumi Okochi
Aug 2, 2018·Physiological Reviews·Yasushi OkamuraTakafumi Kawai
Oct 23, 2019·Cold Spring Harbor Perspectives in Medicine·Glenn R Masson, Roger L Williams
Apr 27, 2018·The Journal of General Physiology·Vamseedhar RayaproluSusy C Kohout
Jan 10, 2019·The Journal of General Physiology·Martin KruseBertil Hille
Oct 28, 2014·Physiological Reports·Joshua MutuaYasushi Okamura
Jun 23, 2016·Proceedings of the National Academy of Sciences of the United States of America·Souhei SakataYasushi Okamura
Jul 11, 2018·Cellular and Molecular Life Sciences : CMLS·Michael G LeitnerChristian R Halaszovich
Oct 10, 2021·Nature Structural & Molecular Biology·Daniel R DempseyPhilip A Cole

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
circular dichroism
gel filtration
Assay

Software Mentioned

MolRep
Clampfit
Excel
IGOR

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.