2jmg: Difference between revisions
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==Solution structure of V7R mutant of HIV-1 myristoylated matrix protein== | |||
<StructureSection load='2jmg' size='340' side='right'caption='[[2jmg]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2jmg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JMG FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jmg OCA], [https://pdbe.org/2jmg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jmg RCSB], [https://www.ebi.ac.uk/pdbsum/2jmg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jmg ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6E183_9HIV1 Q6E183_9HIV1] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jm/2jmg_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jmg ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
During the late phase of human immunodeficiency virus type-1 (HIV-1) replication, newly synthesized retroviral Gag proteins are targeted to lipid raft regions of specific cellular membranes, where they assemble and bud to form new virus particles. Gag binds preferentially to the plasma membrane (PM) of most hematopoietic cell types, a process mediated by interactions between the cellular PM marker phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P(2)) and Gag's N-terminally myristoylated matrix (MA) domain. We recently demonstrated that PI(4,5)P(2) binds to a conserved cleft on MA and promotes myristate exposure, suggesting a role as both a direct membrane anchor and myristyl switch trigger. Here we show that PI(4,5)P(2) is also capable of binding to MA proteins containing point mutations that inhibit membrane binding in vitro, and in vivo, including V7R, L8A and L8I. However, these mutants do not exhibit PI(4,5)P(2) or concentration-dependent myristate exposure. NMR studies of V7R and L8A MA reveal minor structural changes that appear to be responsible for stabilizing the myristate-sequestered (myr(s)) species and inhibiting exposure. Unexpectedly, the myristyl group of a revertant mutant with normal PM targeting properties (V7R,L21K) is also tightly sequestered and insensitive to PI(4,5)P(2) binding. This mutant binds PI(4,5)P(2) with twofold higher affinity compared with the native protein, suggesting a potential compensatory mechanism for membrane binding. | |||
Point mutations in the HIV-1 matrix protein turn off the myristyl switch.,Saad JS, Loeliger E, Luncsford P, Liriano M, Tai J, Kim A, Miller J, Joshi A, Freed EO, Summers MF J Mol Biol. 2007 Feb 16;366(2):574-85. Epub 2006 Dec 1. PMID:17188710<ref>PMID:17188710</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2jmg" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Gag polyprotein|Gag polyprotein]] | *[[Gag polyprotein 3D structures|Gag polyprotein 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Freed | [[Category: Large Structures]] | ||
[[Category: Joshi | [[Category: Freed EO]] | ||
[[Category: Kim | [[Category: Joshi A]] | ||
[[Category: Liriano | [[Category: Kim A]] | ||
[[Category: Loeliger | [[Category: Liriano M]] | ||
[[Category: Luncsford | [[Category: Loeliger E]] | ||
[[Category: Miller | [[Category: Luncsford P]] | ||
[[Category: Saad | [[Category: Miller J]] | ||
[[Category: Summers | [[Category: Saad JS]] | ||
[[Category: Tai | [[Category: Summers MF]] | ||
[[Category: Tai J]] | |||
Latest revision as of 04:06, 21 November 2024
Solution structure of V7R mutant of HIV-1 myristoylated matrix proteinSolution structure of V7R mutant of HIV-1 myristoylated matrix protein
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedDuring the late phase of human immunodeficiency virus type-1 (HIV-1) replication, newly synthesized retroviral Gag proteins are targeted to lipid raft regions of specific cellular membranes, where they assemble and bud to form new virus particles. Gag binds preferentially to the plasma membrane (PM) of most hematopoietic cell types, a process mediated by interactions between the cellular PM marker phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P(2)) and Gag's N-terminally myristoylated matrix (MA) domain. We recently demonstrated that PI(4,5)P(2) binds to a conserved cleft on MA and promotes myristate exposure, suggesting a role as both a direct membrane anchor and myristyl switch trigger. Here we show that PI(4,5)P(2) is also capable of binding to MA proteins containing point mutations that inhibit membrane binding in vitro, and in vivo, including V7R, L8A and L8I. However, these mutants do not exhibit PI(4,5)P(2) or concentration-dependent myristate exposure. NMR studies of V7R and L8A MA reveal minor structural changes that appear to be responsible for stabilizing the myristate-sequestered (myr(s)) species and inhibiting exposure. Unexpectedly, the myristyl group of a revertant mutant with normal PM targeting properties (V7R,L21K) is also tightly sequestered and insensitive to PI(4,5)P(2) binding. This mutant binds PI(4,5)P(2) with twofold higher affinity compared with the native protein, suggesting a potential compensatory mechanism for membrane binding. Point mutations in the HIV-1 matrix protein turn off the myristyl switch.,Saad JS, Loeliger E, Luncsford P, Liriano M, Tai J, Kim A, Miller J, Joshi A, Freed EO, Summers MF J Mol Biol. 2007 Feb 16;366(2):574-85. Epub 2006 Dec 1. PMID:17188710[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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