2h3v
From Proteopedia
(New page: 200px<br /> <applet load="2h3v" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h3v" /> '''Structure of the HIV-1 Matrix protein bound...) |
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'''Structure of the HIV-1 Matrix protein bound to di-C8-phosphatidylinositol-(4,5)-bisphosphate'''<br /> | '''Structure of the HIV-1 Matrix protein bound to di-C8-phosphatidylinositol-(4,5)-bisphosphate'''<br /> | ||
==Overview== | ==Overview== | ||
| - | During the late phase of HIV type 1 (HIV-1) replication, newly synthesized | + | During the late phase of HIV type 1 (HIV-1) replication, newly synthesized retroviral Gag proteins are targeted to the plasma membrane of most hematopoietic cell types, where they colocalize at lipid rafts and assemble into immature virions. Membrane binding is mediated by the matrix (MA) domain of Gag, a 132-residue polypeptide containing an N-terminal myristyl group that can adopt sequestered and exposed conformations. Although exposure is known to promote membrane binding, the mechanism by which Gag is targeted to specific membranes has yet to be established. Recent studies have shown that phosphatidylinositol (PI) 4,5-bisphosphate [PI(4,5)P(2)], a factor that regulates localization of cellular proteins to the plasma membrane, also regulates Gag localization and assembly. Here we show that PI(4,5)P(2) binds directly to HIV-1 MA, inducing a conformational change that triggers myristate exposure. Related phosphatidylinositides PI, PI(3)P, PI(4)P, PI(5)P, and PI(3,5)P(2) do not bind MA with significant affinity or trigger myristate exposure. Structural studies reveal that PI(4,5)P(2) adopts an "extended lipid" conformation, in which the inositol head group and 2'-fatty acid chain bind to a hydrophobic cleft, and the 1'-fatty acid and exposed myristyl group bracket a conserved basic surface patch previously implicated in membrane binding. Our findings indicate that PI(4,5)P(2) acts as both a trigger of the myristyl switch and a membrane anchor and suggest a potential mechanism for targeting Gag to membrane rafts. |
==About this Structure== | ==About this Structure== | ||
| - | 2H3V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with PIO as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2H3V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=PIO:'>PIO</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H3V OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Ghanam, R | + | [[Category: Ghanam, R H.]] |
[[Category: Kim, A.]] | [[Category: Kim, A.]] | ||
[[Category: Miller, J.]] | [[Category: Miller, J.]] | ||
| - | [[Category: Saad, J | + | [[Category: Saad, J S.]] |
| - | [[Category: Summers, M | + | [[Category: Summers, M F.]] |
[[Category: Tai, J.]] | [[Category: Tai, J.]] | ||
[[Category: PIO]] | [[Category: PIO]] | ||
[[Category: hiv-1 unmyristoylated ma protein]] | [[Category: hiv-1 unmyristoylated ma protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:37:54 2008'' |
Revision as of 15:37, 21 February 2008
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Structure of the HIV-1 Matrix protein bound to di-C8-phosphatidylinositol-(4,5)-bisphosphate
Overview
During the late phase of HIV type 1 (HIV-1) replication, newly synthesized retroviral Gag proteins are targeted to the plasma membrane of most hematopoietic cell types, where they colocalize at lipid rafts and assemble into immature virions. Membrane binding is mediated by the matrix (MA) domain of Gag, a 132-residue polypeptide containing an N-terminal myristyl group that can adopt sequestered and exposed conformations. Although exposure is known to promote membrane binding, the mechanism by which Gag is targeted to specific membranes has yet to be established. Recent studies have shown that phosphatidylinositol (PI) 4,5-bisphosphate [PI(4,5)P(2)], a factor that regulates localization of cellular proteins to the plasma membrane, also regulates Gag localization and assembly. Here we show that PI(4,5)P(2) binds directly to HIV-1 MA, inducing a conformational change that triggers myristate exposure. Related phosphatidylinositides PI, PI(3)P, PI(4)P, PI(5)P, and PI(3,5)P(2) do not bind MA with significant affinity or trigger myristate exposure. Structural studies reveal that PI(4,5)P(2) adopts an "extended lipid" conformation, in which the inositol head group and 2'-fatty acid chain bind to a hydrophobic cleft, and the 1'-fatty acid and exposed myristyl group bracket a conserved basic surface patch previously implicated in membrane binding. Our findings indicate that PI(4,5)P(2) acts as both a trigger of the myristyl switch and a membrane anchor and suggest a potential mechanism for targeting Gag to membrane rafts.
About this Structure
2H3V is a Single protein structure of sequence from Human immunodeficiency virus 1 with as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly., Saad JS, Miller J, Tai J, Kim A, Ghanam RH, Summers MF, Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11364-9. Epub 2006 Jul 13. PMID:16840558
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