PDBsum entry 2k4h

Structural protein

PDB id: 2k4h

Contents

Protein chain

134 a.a. *

Ligands

MYR

* Residue conservation analysis

PDB id:

2k4h

Name:

Structural protein

Title:

Solution structure of the HIV-2 myristoylated matrix protein

Structure:

HIV-2 myristoylated matrix protein. Chain: a. Fragment: unp residues 2 to 135. Synonym: matrix protein p17. Engineered: yes

Source:

Human immunodeficiency virus type 2. HIV-2. Organism_taxid: 11720. Strain: prod10. Gene: gag-pol. Expressed in: escherichia coli.

NMR struc:

20 models

Authors:

J.S.Saad,S.D.Ablan,R.H.Ghanam,A.Kim,K.Andrews,K.Nagashima,E.O.Freed, M.F.Summers

Key ref:

J.S.Saad et al. (2008). 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. PubMed id: 18657545 DOI: 10.1016/j.jmb.2008.07.027

Date:

08-Jun-08 Release date: 12-Aug-08

Protein chain

P04584  (POL_HV2RO) -  Gag-Pol polyprotein from Human immunodeficiency virus type 2 subtype A (isolate ROD)

Seq: 1464 a.a.

Struc: 134 a.a.

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.- - ?????
• Enzyme class 2: E.C.2.7.7.49 - RNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 3: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 4: E.C.3.1.-.-
• Enzyme class 5: E.C.3.1.13.2 - exoribonuclease H.
• Reaction: Exonucleolytic cleavage to 5'-phosphomonoester oligonucleotides in both 5'- to 3'- and 3'- to 5'-directions.
• Enzyme class 6: E.C.3.1.26.13 - retroviral ribonuclease H.
• Enzyme class 7: E.C.3.4.23.47 - HIV-2 retropepsin.

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.jmb.2008.07.027

J Mol Biol 382:434-447 (2008)

PubMed id: 18657545

Structure of the myristylated human immunodeficiency virus type 2 matrix protein and the role of phosphatidylinositol-(4,5)-bisphosphate in membrane targeting.

J.S.Saad, S.D.Ablan, R.H.Ghanam, A.Kim, K.Andrews, K.Nagashima, F.Soheilian, E.O.Freed, M.F.Summers.

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.

Selected figure(s)

Figure 4.
Fig. 4. A representative structure of HIV-2 myr(+)MA (slate) and comparison with the HIV-1 myr(+)MA protein (sand). (a) Semitransparent surface representation of MA showing the penetration of the myr group (red sticks) and interactions with the side chains of Val7, Leu8, Leu16, Ile34, and ILe85 (green sticks). (b) Cartoon representation of the HIV-2 and HIV-1 myr(+)MA proteins comparing the sequestration of the myristate group (red) in the hydrophobic cavity formed by residues Val7, Leu8, Leu16, Ile34, and Ile85 (green spheres). (c) Superimposition of representative structures of HIV-2 and HIV-1 myr(+)MA. Myristate groups of HIV-2 and HIV-1 myr(+)MA proteins are packing against Leu16 and Trp16, respectively. NMR data revealed that helix 6 is flexible for both proteins. (d) An expanded view of the protein core of HIV-2 and HIV-1 myr(+)MA showing the myristate packing against side chains of Leu16 and Trp16, respectively.

Figure 7.
Fig. 7. Structure of the HIV-2 myr(+)MA/di-C[4]-PI(4,5)P[2] complex. (a,b) Interactions between di-C[4]-PI(4,5)P[2] (sticks) and MA (colored according to electrostatic surface potential) showing the 2′-fatty acid inserting in a preexisting cleft and the inositol ring packing against a basic patch of the protein. (c) PI(4,5)P[2] binding to the β-II–V cleft. (d) A network of interactions implicated in PI(4,5)P[2] binding.

The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2008, 382, 434-447) copyright 2008.

Figures were selected by the author.