Structural Basis for the 14-3-3 Protein-Dependent Inhibition of Phosducin Function

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F17%3A00475511" target="_blank" >RIV/67985823:_____/17:00475511 - isvavai.cz</a>

Alternative codes found

RIV/61388971:_____/17:00475511 RIV/00216208:11310/17:10364663 RIV/00216224:14740/17:00100398

Result on the web

<a href="http://dx.doi.org/10.1016/j.bpj.2017.02.036" target="_blank" >http://dx.doi.org/10.1016/j.bpj.2017.02.036</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bpj.2017.02.036" target="_blank" >10.1016/j.bpj.2017.02.036</a>

Result language

angličtina

Original language name

Structural Basis for the 14-3-3 Protein-Dependent Inhibition of Phosducin Function

Original language description

Phosducin (Pdc) is a conserved phosphoprotein that, when unphosphorylated, binds with high affinity to the complex of beta gamma subunits of G protein transducin. The ability of Pdc to bind to Gt(beta gamma) is inhibited through its phosphorylation at S54 andS73 within the N-terminal domain (Pdc-ND) followed by association with the scaffolding protein 14-3-3. However, the molecular basis for the 14-3-3-dependent inhibition of Pdc binding to Gt(beta gamma) is unclear. By using small-angle x-ray scattering, high-resolution NMR spectroscopy, and limited proteolysis coupled with mass spectrometry, we show that phosphorylated Pdc and 14-3-3 forma complex in which the Pdc-ND region 45-80, which forms a part of Pdc's Gt(beta gamma) binding surface and contains both phosphorylation sites, is restrained within the central channel of the 14-3-3 dimer, with both 14-3-3 binding motifs simultaneously participating in protein association. The N-terminal part of Pdc-NDis likely located outside the central channel of the 14-3-3 dimer, but Pdc residues 20-30, which are also involved in Gt(beta gamma) binding, are positioned close to the surface of the 14-3-3 dimer. The C-terminal domain of Pdc is located outside the central channel and its structure is unaffected by the complex formation. These results indicate that the 14-3-3 protein-mediated inhibition of Pdc binding to Gt(beta gamma) is based on steric occlusion of Pdc's Gt(beta gamma) binding surface.

Czech name

—

Czech description

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Type

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

CEP classification

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OECD FORD branch

10609 - Biochemical research methods

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

Biophysical Journal

ISSN

0006-3495

e-ISSN

—

Volume of the periodical

112

Issue of the periodical within the volume

7

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

1339-1349

UT code for WoS article

000398956000007

EID of the result in the Scopus database

2-s2.0-85017311104