Binding of equine infectious anemia virus matrix protein to membrane bilayers involves multiple interactions.
Abstract: Human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) are closely related lentiviruses that infect immune cells, but their pathogenesis differ. Localization to the cytosolic leaflet of the plasma membrane is critical for replication of both viruses. This localization is accomplished through the matrix (MA) domain of the Gag precursor protein. In HIV-1, association of MA to anionic membranes appears to be primarily driven by a linear cluster of basic residues in the MA domain and an N-myristoylation signal. Interestingly, the MA protein of EIAV does not contain either of these signals. To understand which factors could promote EIAV assembly we characterized the membrane binding properties of its MA protein using fluorescence and biochemical methods. We find that EIAV MA exists as a multimer in solution whose protein-protein interactions are destabilized by membrane binding. EIAV MA binds strongly to electrically neutral membranes as well as to negatively charged membranes. Fluorescence quenching and chemical modification techniques, as well as trypsin proteolysis, indicate a different exposure of the EIAV MA Trp residues when bound to the two types of membranes, and EIAV MA proteolysis by trypsin differs when bound to the two types of membranes. Based on these data and the known structures of closely related matrix proteins, we constructed a structural model. This model predicts that EIAV MA binds to negatively charged membranes, but EIAV MA has an additional membrane binding region rich in residues that partition favorably into the membrane headgroup region. This secondary site may play a role in early events of viral infection.
Copyright 2000 Academic Press.
Publication Date: 2000-03-15 PubMed ID: 10677289DOI: 10.1006/jmbi.1999.3482Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research focuses on the equine infectious anemia virus (EIAV) and how the matrix (MA) protein of this virus interacts with the membrane of host cells. This understanding is crucial for decoding viral pathogenesis and potentially developing treatment strategies.
Background of the Study
- The research starts by drawing links to the human immunodeficiency virus (HIV) and the equine infectious anemia virus (EIAV), both of which are lentiviruses that infect immune cells.
- The study emphasizes the importance of viral localization on the cytosolic leaflet of the plasma membrane for successful replication of both viruses.
- In HIV-1, the association of the matrix protein to anionic membranes is critical and is facilitated by basic residues and N-myristoylation signals. However, in EIAV, these facilitating signals are absent, which sparked the curiosity to understand how EIAV assembly takes place.
Research Methodology
- To determine the factors promoting EIAV assembly, the membrane binding properties of the EIAV MA protein were studied using fluorescence and biochemical methods.
- The researchers also analyzed the interaction between EIAV MA and different types of membranes – electrically neutral and negatively charged ones. Different techniques like fluorescence quenching and chemical modification were used to understand this interaction.
Key Findings
- The findings revealed that the EIAV MA protein exists as a multimer in solution and the protein-protein interactions were destabilized by binding to the membrane.
- It was also observed that EIAV MA binds strongly to both electrically neutral and negatively charged membranes, indicating a different mode of action than HIV-1.
- The exposure of the EIAV MA Trp residues was different between two types of membranes. Further, proteolysis of EIAV MA by trypsin varied when bound to neutral or charged membranes.
Study Outcomes and Implications
- The data gathered from this research was used to create a structural model predicting that EIAV MA binds to negatively charged membranes. Additionally, EIAV has another membrane binding region rich in residues that can enter into the membrane headgroup region favorably.
- The research team suggested that this secondary binding site might play a crucial role in the early events of viral infection.
- This study contributes a greater understanding of the distinct ways in which EIAV operates compared to other lentiviruses such as HIV. This deep insight opens up potential avenues for developing targeted therapeutic interventions against EIAV.
Cite This Article
APA
Provitera P, Bouamr F, Murray D, Carter C, Scarlata S.
(2000).
Binding of equine infectious anemia virus matrix protein to membrane bilayers involves multiple interactions.
J Mol Biol, 296(3), 887-898.
https://doi.org/10.1006/jmbi.1999.3482 Publication
Researcher Affiliations
- Department of Physiology, State University of New York at Stony Brook, 11794-8661, USA.
MeSH Terms
- Amino Acid Sequence
- Cell Membrane / chemistry
- Cell Membrane / metabolism
- Fluorescence
- Fluorescence Polarization
- Infectious Anemia Virus, Equine
- Lipid Bilayers / chemistry
- Lipid Bilayers / metabolism
- Models, Molecular
- Molecular Sequence Data
- Phosphatidylcholines / metabolism
- Phosphatidylserines / metabolism
- Protein Binding
- Recombinant Fusion Proteins / metabolism
- Sequence Alignment
- Solutions
- Static Electricity
- Thermodynamics
- Trypsin / metabolism
- Viral Matrix Proteins / metabolism
- Virus Assembly
Grant Funding
- GM58271 / NIGMS NIH HHS
Citations
This article has been cited 19 times.- Junková P, Pleskot R, Prchal J, Sýs J, Ruml T. Differences and commonalities in plasma membrane recruitment of the two morphogenetically distinct retroviruses HIV-1 and MMTV.. J Biol Chem 2020 Jun 26;295(26):8819-8833.
- Vlach J, Eastep GN, Ghanam RH, Watanabe SM, Carter CA, Saad JS. Structural basis for targeting avian sarcoma virus Gag polyprotein to the plasma membrane for virus assembly.. J Biol Chem 2018 Dec 7;293(49):18828-18840.
- Folio C, Sierra N, Dujardin M, Alvarez G, Guillon C. Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein Shows an N-Terminal β-Hairpin in the Absence of N-Terminal Proline.. Viruses 2017 Nov 9;9(11).
- Vlach J, Saad JS. Structural and molecular determinants of HIV-1 Gag binding to the plasma membrane.. Front Microbiol 2015;6:232.
- Alfadhli A, Barklis E. The roles of lipids and nucleic acids in HIV-1 assembly.. Front Microbiol 2014;5:253.
- Vlach J, Saad JS. Trio engagement via plasma membrane phospholipids and the myristoyl moiety governs HIV-1 matrix binding to bilayers.. Proc Natl Acad Sci U S A 2013 Feb 26;110(9):3525-30.
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- Chan J, Dick RA, Vogt VM. Rous sarcoma virus gag has no specific requirement for phosphatidylinositol-(4,5)-bisphosphate for plasma membrane association in vivo or for liposome interaction in vitro.. J Virol 2011 Oct;85(20):10851-60.
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- Fernandes F, Chen K, Ehrlich LS, Jin J, Chen MH, Medina GN, Symons M, Montelaro R, Donaldson J, Tjandra N, Carter CA. Phosphoinositides direct equine infectious anemia virus gag trafficking and release.. Traffic 2011 Apr;12(4):438-51.
- Ballin JD, Prevas JP, Bharill S, Gryczynski I, Gryczynski Z, Wilson GM. Local RNA conformational dynamics revealed by 2-aminopurine solvent accessibility.. Biochemistry 2008 Jul 8;47(27):7043-52.
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- Scianimanico S, Schoehn G, Timmins J, Ruigrok RH, Klenk HD, Weissenhorn W. Membrane association induces a conformational change in the Ebola virus matrix protein.. EMBO J 2000 Dec 15;19(24):6732-41.
- Dessen A, Volchkov V, Dolnik O, Klenk HD, Weissenhorn W. Crystal structure of the matrix protein VP40 from Ebola virus.. EMBO J 2000 Aug 15;19(16):4228-36.
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