1UPH

HIV-1 Myristoylated Matrix

Summary for 1UPH

• Entry DOI: 10.2210/pdb1uph/pdb
• Related: 1A43 1A8O 1AFV 1AK4 1AUM 1BAJ 1GDS 1GDY 1GDZ 1GWP 1HIW 1L6N 2HMX
• Descriptor: GAG POLYPROTEIN (1 entity in total)
• Functional Keywords: virus/viral protein, myristyl, myristoylated, post-translational modification, myristyl switch, polyprotein, phosphorylation, virus-viral protein complex
• Biological source: HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (CLONE 12) (HIV-1)
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential): P12493
• Total number of polymer chains: 1
• Total formula weight: 14944.97

Authors

Tang, C.,Loeliger, E.,Luncsford, P.,Kinde, I.,Beckett, D.,Summers, M.F. (deposition date: 2003-10-01, release date: 2004-01-08, Last modification date: 2025-04-09)

Primary citation

Tang, C.,Loeliger, E.,Luncsford, P.,Kinde, I.,Beckett, D.,Summers, M.F.
Entropic Switch Regulates Myristate Exposure in the HIV-1 Matrix Protein
Proc.Natl.Acad.Sci.USA, 101:517-, 2004

PubMed Abstract: The myristoylated matrix protein (myr-MA) of HIV functions as a regulator of intracellular localization, targeting the Gag precursor polyprotein to lipid rafts in the plasma membrane during virus assembly and dissociating from the membrane during infectivity for nuclear targeting of the preintegration complex. Membrane release is triggered by proteolytic cleavage of Gag, and it has, until now, been believed that proteolysis induces a conformational change in myr-MA that sequesters the myristyl group. NMR studies reported here reveal that myr-MA adopts myr-exposed [myr(e)] and -sequestered [myr(s)] states, as anticipated. Unexpectedly, the tertiary structures of the protein in both states are very similar, with the sequestered myristyl group occupying a cavity that requires only minor conformational adjustments for insertion. In addition, myristate exposure is coupled with trimerization, with the myristyl group sequestered in the monomer and exposed in the trimer (K(assoc) = 2.5 +/- 0.6 x 10(8) M(-2)). The equilibrium constant is shifted approximately 20-fold toward the trimeric, myristate-exposed species in a Gag-like construct that includes the capsid domain, indicating that exposure is enhanced by Gag subdomains that promote self-association. Our findings indicate that the HIV-1 myristyl switch is regulated not by mechanically induced conformational changes, as observed for other myristyl switches, but instead by entropic modulation of a preexisting equilibrium.

PubMed: 14699046
DOI: 10.1073/PNAS.0305665101

Experimental method

SOLUTION NMR