2K4H

Solution structure of the HIV-2 myristoylated Matrix protein

Summary for 2K4H

• Entry DOI: 10.2210/pdb2k4h/pdb
• Related: 2K4E 2K4I
• NMR Information: BMRB: 16888
• Descriptor: HIV-2 myristoylated matrix protein, MYRISTIC ACID (2 entities in total)
• Functional Keywords: aids, capsid protein, myristate, matrix, gag, hiv, virion, structural protein, plasma membrane
• Biological source: Human immunodeficiency virus type 2 (HIV-2)
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P04584
• Total number of polymer chains: 1
• Total formula weight: 15127.63

Authors

Saad, J.S.,Ablan, S.D.,Ghanam, R.H.,Kim, A.,Andrews, K.,Nagashima, K.,Freed, E.O.,Summers, M.F. (deposition date: 2008-06-08, release date: 2008-08-12, Last modification date: 2024-10-30)

Primary citation

Saad, J.S.,Ablan, S.D.,Ghanam, R.H.,Kim, A.,Andrews, K.,Nagashima, K.,Soheilian, F.,Freed, E.O.,Summers, M.F.
Structure of the myristylated human immunodeficiency virus type 2 matrix protein and the role of phosphatidylinositol-(4,5)-bisphosphate in membrane targeting.
J.Mol.Biol., 382:434-447, 2008

PubMed Abstract: During the late phase of retroviral replication, newly synthesized Gag proteins are targeted to the plasma membrane (PM), where they assemble and bud to form immature virus particles. Membrane targeting by human immunodeficiency virus type 1 (HIV-1) Gag is mediated by the PM marker molecule phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)], which is capable of binding to the matrix (MA) domain of Gag in an extended lipid conformation and of triggering myristate exposure. Here, we show that, as observed previously for HIV-1 MA, the myristyl group of HIV-2 MA is partially sequestered within a narrow hydrophobic tunnel formed by side chains of helices 1, 2, 3, and 5. However, the myristate of HIV-2 MA is more tightly sequestered than that of the HIV-1 protein and does not exhibit concentration-dependent exposure. Soluble PI(4,5)P(2) analogs containing truncated acyl chains bind HIV-2 MA and induce minor long-range structural changes but do not trigger myristate exposure. Despite these differences, the site of HIV-2 assembly in vivo can be manipulated by enzymes that regulate PI(4,5)P(2) localization. Our findings indicate that HIV-1 and HIV-2 are both targeted to the PM for assembly via a PI(4,5)P(2)-dependent mechanism, despite differences in the sensitivity of the MA myristyl switch, and suggest a potential mechanism that may contribute to the poor replication kinetics of HIV-2.

PubMed: 18657545
DOI: 10.1016/j.jmb.2008.07.027

Experimental method

SOLUTION NMR