2m7w: Difference between revisions
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== | ==Independently verified structure of gp41-M-MAT, a membrane associated MPER trimer from HIV-1 gp41== | ||
[[2m7w]] is a 3 chain structure with sequence from [ | <StructureSection load='2m7w' size='340' side='right'caption='[[2m7w]]' scene=''> | ||
[[ | == Structural highlights == | ||
[[ | <table><tr><td colspan='2'>[[2m7w]] is a 3 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=2M7W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M7W FirstGlance]. <br> | ||
[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | ||
[[Category: | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2m7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m7w OCA], [https://pdbe.org/2m7w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m7w RCSB], [https://www.ebi.ac.uk/pdbsum/2m7w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m7w ProSAT]</span></td></tr> | ||
[[Category: | </table> | ||
[[Category: | == Function == | ||
[[Category: | [https://www.uniprot.org/uniprot/M1E1E4_9HIV1 M1E1E4_9HIV1] | ||
[[Category: | <div style="background-color:#fffaf0;"> | ||
[[Category: | == Publication Abstract from PubMed == | ||
[[Category: | The membrane proximal external region (MPER) of HIV-1 glycoprotein (gp) 41 is involved in viral-host cell membrane fusion. It contains short amino acid sequences that are binding sites for the HIV-1 broadly neutralizing antibodies 2F5, 4E10, and 10E8, making these binding sites important targets for HIV-1 vaccine development. We report a high-resolution structure of a designed MPER trimer assembled on a detergent micelle. The NMR solution structure of this trimeric domain, designated gp41-M-MAT, shows that the three MPER peptides each adopt symmetric alpha-helical conformations exposing the amino acid side chains of the antibody binding sites. The helices are closely associated at their N termini, bend between the 2F5 and 4E10 epitopes, and gradually separate toward the C termini, where they associate with the membrane. The mAbs 2F5 and 4E10 bind gp41-M-MAT with nanomolar affinities, consistent with the substantial exposure of their respective epitopes in the trimer structure. The traditional structure determination of gp41-M-MAT using the Xplor-NIH protocol was validated by independently determining the structure using the DISCO sparse-data protocol, which exploits geometric arrangement algorithms that guarantee to compute all structures and assignments that satisfy the data. | ||
[[Category: | |||
[[Category: | Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer.,Reardon PN, Sage H, Dennison SM, Martin JW, Donald BR, Alam SM, Haynes BF, Spicer LD Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1391-6. doi:, 10.1073/pnas.1309842111. Epub 2014 Jan 13. PMID:24474763<ref>PMID:24474763</ref> | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2m7w" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human immunodeficiency virus 1]] | |||
[[Category: Large Structures]] | |||
[[Category: Donald BR]] | |||
[[Category: Haynes BF]] | |||
[[Category: Martin JW]] | |||
[[Category: Moses DS]] | |||
[[Category: Munir AS]] | |||
[[Category: Reardon PN]] | |||
[[Category: Sage HS]] | |||
[[Category: Spicer LD]] | |||
Latest revision as of 09:01, 15 May 2024
Independently verified structure of gp41-M-MAT, a membrane associated MPER trimer from HIV-1 gp41Independently verified structure of gp41-M-MAT, a membrane associated MPER trimer from HIV-1 gp41
Structural highlights
FunctionPublication Abstract from PubMedThe membrane proximal external region (MPER) of HIV-1 glycoprotein (gp) 41 is involved in viral-host cell membrane fusion. It contains short amino acid sequences that are binding sites for the HIV-1 broadly neutralizing antibodies 2F5, 4E10, and 10E8, making these binding sites important targets for HIV-1 vaccine development. We report a high-resolution structure of a designed MPER trimer assembled on a detergent micelle. The NMR solution structure of this trimeric domain, designated gp41-M-MAT, shows that the three MPER peptides each adopt symmetric alpha-helical conformations exposing the amino acid side chains of the antibody binding sites. The helices are closely associated at their N termini, bend between the 2F5 and 4E10 epitopes, and gradually separate toward the C termini, where they associate with the membrane. The mAbs 2F5 and 4E10 bind gp41-M-MAT with nanomolar affinities, consistent with the substantial exposure of their respective epitopes in the trimer structure. The traditional structure determination of gp41-M-MAT using the Xplor-NIH protocol was validated by independently determining the structure using the DISCO sparse-data protocol, which exploits geometric arrangement algorithms that guarantee to compute all structures and assignments that satisfy the data. Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer.,Reardon PN, Sage H, Dennison SM, Martin JW, Donald BR, Alam SM, Haynes BF, Spicer LD Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1391-6. doi:, 10.1073/pnas.1309842111. Epub 2014 Jan 13. PMID:24474763[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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