Aromatic amino acids and their relevance in the specificity of the PH domain

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F17%3A00486692" target="_blank" >RIV/68378050:_____/17:00486692 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1002/jmr.2649" target="_blank" >http://dx.doi.org/10.1002/jmr.2649</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/jmr.2649" target="_blank" >10.1002/jmr.2649</a>

Result language

angličtina

Original language name

Aromatic amino acids and their relevance in the specificity of the PH domain

Original language description

Phosphoinositides are phosphatidylinositol derived, well known to be second messengers in various cell signaling pathways as well as in processes such as cell differentiation, cellular stress response, gene transcription, and chromatin remodeling. The pleckstrin homology domain of phospholipase C-delta 1 is responsible for recognizing and binding to PI(4,5) P-2 and for this reason has been widely used to study this phosphoinositide as a biosensor when it is conjugated to a fluorescent tag. In this work, we modified the primary structure of pleckstrin homology domain by site-specific mutagenesis to change the specificity for phosphoinositides. We obtained 3 mutants: K30A, W36F, and W36Y with different specificity to phosphoinositides. Mutant domain K30A recognized PI(4,5) P-2, PI(3,4,5) P-3, phosphatidic acid (PA), and weakly PI(3,5) P-2. Mutant domain W36F recognized all the phosphoinositides studied and the PA. Finally, mutant domain W36Y seemed to interact with PA and all the other phosphoinositides studied, except PI(3) P. The changes in recognition argue against a simple charge and nonpolar region model for these interactions and more in favor of a specific docking region with a specific recognition site. We conducted in silico modeling that explains the mechanisms behind the observed changes and showed that aromatic amino acids appear to play more important role, than previously thought, in the specificity of phospholipids' binding domains.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Molecular Recognition

ISSN

0952-3499

e-ISSN

—

Volume of the periodical

30

Issue of the periodical within the volume

12

Country of publishing house

GB - UNITED KINGDOM

Number of pages

7

Pages from-to

—

UT code for WoS article

000418743800003

EID of the result in the Scopus database

—