Interaction of Mason-Pfizer Monkey Virus Matrix Protein with Calmodulin: Effects on the Late-Phase of Retroviral Life Cycle

Result code in IS VaVaI

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Alternative codes found

RIV/60461373:22810/25:43931948

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Interaction of Mason-Pfizer Monkey Virus Matrix Protein with Calmodulin: Effects on the Late-Phase of Retroviral Life Cycle

Original language description

Calmodulin (CaM), a ubiquitous cellular protein, plays a critical role in regulating various cellular processes through calcium-induced conformational changes. Its involvement in the life cycle of many viruses, including retroviruses, is well documented. In HIV-1-infected cells, CaM concentration is significantly elevated compared to uninfected cells. The structural polyprotein Gag of HIV-1 interacts with CaM via its N-terminal matrix (MA) domain, a region crucial for viral targeting to the plasma membrane (PM). This interaction induces a myristoyl (myr) switch in the MA protein, exposing its N-terminal myristoyl group, which facilitates membrane binding.We extended this investigation to the Mason-Pfizer monkey virus (M-PMV), a retrovirus with distinct late-phase life cycle mechanisms. HIV-1 assembles at the plasma membrane (PM), whereas M-PMV assembles in the cytoplasm. Our co-immunoprecipitation experiments successfully demonstrated the interaction of M-PMV Gag with HA-tagged human calmodulin in HEK 293T cell lysates. This interaction was confirmed to be Ca²⁺-dependent in both in vivo and in vitro settings.Further characterization of the interaction was conducted using microscale thermophoresis, protein cross-linking coupled with mass spectrometry, and liposome binding assay. Additionally, MA mutants were engineered to assess their impact on the presence and parameters of the interaction. Our findings provide valuable insights, suggesting a potentially significant role for the MA-CaM interaction in regulating key steps of the late phase of the retroviral life cycle.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10607 - Virology

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

2025

Confidentiality

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