A glutamate switch controls voltage-sensitive phosphatase function
| Autor: | Susy C. Kohout, Ehud Y. Isacoff, Christopher R. Kimberlin, Qiang Xu, Lijun Liu, Daniel L. Minor, Simone Müller |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Protein Conformation Molecular Sequence Data Phosphatase Glutamic Acid Voltage sensitive phosphatase Gating Crystallography X-Ray Article 03 medical and health sciences Enzyme activator 0302 clinical medicine Protein structure Structural Biology Animals Humans Amino Acid Sequence Molecular Biology 030304 developmental biology 0303 health sciences biology PTEN Phosphohydrolase Glutamate receptor Active site Glutamic acid Phosphoric Monoester Hydrolases Ciona intestinalis Protein Structure Tertiary Enzyme Activation Biochemistry Mutation biology.protein Biophysics 030217 neurology & neurosurgery |
| Zdroj: | Minor, Daniel; Liu, L; Kohout, SC; Xu, Q; Müller, S; Kimberlin, CR; et al.(2012). A glutamate switch controls voltage-sensitive phosphatase function. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/1c74r865 Nature structural & molecular biology |
| ISSN: | 1545-9985 1545-9993 |
| DOI: | 10.1038/nsmb.2289 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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