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Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: July 1, 2013
The protein network of HIV budding
Uta K von Schwedler1, Melissa Stuchell, Barbara Müller
1Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
Cell
|September 25, 2003
Summary
Viral release, including HIV, depends on cellular proteins that form multivesicular bodies (MVBs). A network of human class E proteins, crucial for MVB biogenesis, is essential for HIV particle budding and release.
Area of Science:
- Cell Biology
- Virology
- Molecular Biology
Background:
- Human Immunodeficiency Virus (HIV) release is dependent on the cellular protein TSG101.
- TSG101 sorts proteins into multivesicular bodies (MVBs), which are involved in HIV budding.
- The role of other proteins involved in MVB biogenesis in HIV release remains unclear.
Purpose of the Study:
- To investigate whether other human class E proteins, involved in MVB biogenesis, participate in HIV release.
- To elucidate the protein-protein interaction network of human class E proteins.
- To determine the direct involvement of these proteins in the viral budding process.
Main Methods:
- Identification of 22 candidate human class E proteins.
- Analysis of protein-protein interactions to map the network.
- Testing the binding of specific proteins to viral Gag proteins.
- Expression of dominant-negative mutants to assess impact on HIV budding.
Main Results:
- A coherent network of 22 human class E proteins was identified, linked by 43 interactions.
- AIP1 was found to be a key linker between early (TSG101/ESCRT-I) and late (CHMP4/ESCRT-III) pathway complexes.
- AIP1 directly binds HIV-1 p6(Gag) and EIAV p9(Gag) proteins.
- Human class E proteins were detected in HIV-1 particles.
- Dominant-negative mutants of late-acting class E proteins inhibited HIV-1 budding.
Conclusions:
- A protein network essential for human MVB biogenesis has been defined.
- This entire network participates in the release of HIV.
- The findings suggest that this MVB biogenesis network is likely involved in the release of many other viruses.
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