Myristoylation drives dimerization of matrix protein from mouse mammary tumor virus

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00458491" target="_blank" >RIV/61388963:_____/16:00458491 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/16:10323073

Result on the web

<a href="http://retrovirology.biomedcentral.com/articles/10.1186/s12977-015-0235-8" target="_blank" >http://retrovirology.biomedcentral.com/articles/10.1186/s12977-015-0235-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12977-015-0235-8" target="_blank" >10.1186/s12977-015-0235-8</a>

Result language

angličtina

Original language name

Myristoylation drives dimerization of matrix protein from mouse mammary tumor virus

Original language description

Background: Myristoylation of the matrix (MA) domain mediates the transport and binding of Gag polyproteins to the plasma membrane (PM) and is required for the assembly of most retroviruses. In betaretroviruses, which assemble immature particles in the cytoplasm, myristoylation is dispensable for assembly but is crucial for particle transport to the PM. Oligomerization of HIV-1 MA stimulates the transition of the myristoyl group from a sequestered to an exposed conformation, which is more accessible for membrane binding. However, for other retroviruses, the effect of MA oligomerization on myristoyl group exposure has not been thoroughly investigated.nResults: Here, we demonstrate that MA from the betaretrovirus mouse mammary tumor virus (MMTV) forms dimers in solution and that this process is stimulated by its myristoylation. The crystal structure of N-myristoylated MMTV MA, determined at 1.57 angstrom resolution, revealed that the myristoyl groups are buried in a hydrophobic pocket at the dimer interface and contribute to dimer formation. Interestingly, the myristoyl groups in the dimer are mutually swapped to achieve energetically stable binding, as documented by molecular dynamics modeling. Mutations within the myristoyl binding site resulted in reduced MA dimerization and extracellular particle release.nConclusions: Based on our experimental, structural, and computational data, we propose a model for dimerization of MMTV MA in which myristoyl groups stimulate the interaction between MA molecules. Moreover, dimer-forming MA molecules adopt a sequestered conformation with their myristoyl groups entirely buried within the interaction interface. Although this differs from the current model proposed for lentiviruses, in which oligomerization of MA triggers exposure of myristoyl group, it appears convenient for intracellular assembly, which involves no apparent membrane interaction and allows the myristoyl group to be sequestered during oligomerization.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

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

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

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

Name of the periodical

Retrovirology

ISSN

1742-4690

e-ISSN

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Volume of the periodical

13

Issue of the periodical within the volume

Jan 5

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

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UT code for WoS article

000367578800001

EID of the result in the Scopus database

2-s2.0-84959132839