Retroviral matrix domains share electrostatic homology: models for membrane binding function throughout the viral life cycle.
The matrix domain (MA) of Gag polyproteins performs multiple functions throughout the retroviral life cycle. MA structures have an electropositive surface patch that is implicated in membrane association. Here, we use computational methods to demonstrate that electrostatic control of membrane binding is a central characteristic of all retroviruses. We are able to explain a wide range of experimental observations and provide a level of quantitative and molecular detail that has been inaccessible to experiment. We further predict that MA may exist in a variety of oligomerization states and propose mechanistic models for the effects of phosphoinositides and phosphorylation. The calculations provide a conceptual model for how non-myristoylated and myristoylated MAs behave similarly in assembly and disassembly. Hence, they provide a unified quantitative picture of the structural and energetic origins of the entire range of MA function and thus enhance, extend, and integrate previous observations on individual stages of the process.
Murray
Paul S
PS
Department of Microbiology and Immunology and The Institute for Computational Biomedicine, Weill Medical College of Cornell, New York, New York 10021, USA.
Li
Zhaohui
Z
Wang
Jiyao
J
Tang
Chris L
CL
Honig
Barry
B
Murray
Diana
D
D002462:Cell Membrane / Q000378:metabolism*; D003198:Computer Simulation; D015683:Gene Products, gag / Q000737:chemistry* / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D019814:Myristic Acid / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000737:chemistry* / Q000502:physiology*; D055672:Static Electricity; D014763:Viral Matrix Proteins / Q000378:metabolism*
D015683:Gene Products, gag; D008051:Lipid Bilayers; D010716:Phosphatidylinositols; D014763:Viral Matrix Proteins; D019814:Myristic Acid