2h3q: Difference between revisions

Line 1:

[[Image:2h3q.gif|left|200px]]<br />

[[Image:2h3q.gif|left|200px]]<br /><applet load="2h3q" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="2h3q" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="2h3q" />

'''Solution structure of HIV-1 myrMA bound to di-C4-phosphatidylinositol-(4,5)-bisphosphate'''<br />

==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.

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==

2H3Q 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 MYR and PBU as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2H3Q OCA].

2H3Q 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=MYR:'>MYR</scene> and <scene name='pdbligand=PBU:'>PBU</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H3Q OCA].

==Reference==

Line 14:

Line 13:

[[Category: Human immunodeficiency virus 1]]

[[Category: Single protein]]

[[Category: Ghanam, R.H.]]

[[Category: Ghanam, R H.]]

[[Category: Kim, A.]]

[[Category: Miller, J.]]

[[Category: Saad, J.S.]]

[[Category: Saad, J S.]]

[[Category: Summers, M.F.]]

[[Category: Summers, M F.]]

[[Category: Tai, J.]]

[[Category: MYR]]

Line 25:

Line 24:

[[Category: hiv-1 myristoylated matrix protein bound to di-c4-pi(4]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on Thu ~~Nov 8 14~~:49:~~22 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:37:53 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-[[Image:2h3q.gif|left|200px]]<br />
+[[Image:2h3q.gif|left|200px]]<br /><applet load="2h3q" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="2h3q" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="2h3q" />
 '''Solution structure of HIV-1 myrMA bound to di-C4-phosphatidylinositol-(4,5)-bisphosphate'''<br />
 ==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.
+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==
-H3Q 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 MYR and PBU as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2H3Q OCA].
+H3Q 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=MYR:'>MYR</scene> and <scene name='pdbligand=PBU:'>PBU</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H3Q OCA].
 ==Reference==
@@ Line 14: / Line 13: @@
 [[Category: Human immunodeficiency virus 1]]
 [[Category: Single protein]]
-[[Category: Ghanam, R.H.]]
+[[Category: Ghanam, R H.]]
 [[Category: Kim, A.]]
 [[Category: Miller, J.]]
-[[Category: Saad, J.S.]]
+[[Category: Saad, J S.]]
-[[Category: Summers, M.F.]]
+[[Category: Summers, M F.]]
 [[Category: Tai, J.]]
 [[Category: MYR]]
@@ Line 25: / Line 24: @@
 [[Category: hiv-1 myristoylated matrix protein bound to di-c4-pi(4]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 14:49:22 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:37:53 2008''