5n88: Difference between revisions
New page: '''Unreleased structure''' The entry 5n88 is ON HOLD Authors: Bao, L., Hannon, C., Cruz-Migoni, A., Ptchelkine, D., Sun, M.-y., Derveni, M., Bunjobpol, W., Chambers, J.S., Simmons, A., ... |
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The | ==Crystal structure of antibody bound to viral protein== | ||
<StructureSection load='5n88' size='340' side='right'caption='[[5n88]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5n88]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N88 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N88 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</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=5n88 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n88 OCA], [https://pdbe.org/5n88 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n88 RCSB], [https://www.ebi.ac.uk/pdbsum/5n88 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n88 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/PSIP1_HUMAN PSIP1_HUMAN] Note=A chromosomal aberration involving PSIP1 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1/LEDGF exon 4. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PSIP1_HUMAN PSIP1_HUMAN] Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.<ref>PMID:15642333</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Preventing the protein-protein interaction of the cellular chromatin binding protein Lens Epithelium-Derived Growth Factor (LEDGF) and human immunodeficiency virus (HIV) integrase is an important possible strategy for anti-viral treatment for AIDS. We have used Intracellular Antibody Capture technology to isolate a single VH antibody domain that binds to LEDGF. The crystal structure of the LEDGF-VH complex reveals that the single domain antibody mimics the effect of binding of HIV integrase to LEDGF which is crucial for HIV propagation. CD4-expressing T cell lines were constructed to constitutively express the LEDGF-binding VH and these cells showed interference with HIV viral replication, assayed by virus capsid protein p24 production. Therefore, pre-conditioning cells to express antibody fragments confers effective intracellular immunization for preventing chronic viral replication and can be a way to prevent HIV spread in infected patients. This raises the prospect that intracellular immunization strategies that focus on cellular components of viral integrase protein interactions can be used to combat the problems associated with latent HIV virus re-emergence in patients. New genome editing development, such as using CRISPR/cas9, offer the prospect intracellularly immunized T cells in HIV+ patients. | |||
Intracellular immunization against HIV infection with an intracellular antibody that mimics HIV integrase binding to the cellular LEDGF protein.,Bao L, Hannon C, Cruz-Mignoni A, Ptchelkine D, Sun MY, Miller A, Bunjobpol W, Quevedo CE, Derveni M, Chambers J, Simmons A, Phillips SEV, Rabbitts TH Sci Rep. 2017 Dec 4;7(1):16869. doi: 10.1038/s41598-017-16742-2. PMID:29203900<ref>PMID:29203900</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5n88" style="background-color:#fffaf0;"></div> | ||
[[Category: Bao | |||
[[Category: Chambers | ==See Also== | ||
[[Category: | *[[Antibody 3D structures|Antibody 3D structures]] | ||
[[Category: | *[[3D structures of human antibody|3D structures of human antibody]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bao L]] | |||
[[Category: Bunjobpol W]] | |||
[[Category: Chambers JS]] | |||
[[Category: Cruz-Migoni A]] | |||
[[Category: Derveni M]] | |||
[[Category: Hannon C]] | |||
[[Category: Phillips SEV]] | |||
[[Category: Ptchelkine D]] | |||
[[Category: Rabbitts TH]] | |||
[[Category: Simmons A]] | |||
[[Category: Sun M-y]] | |||
Latest revision as of 15:34, 15 November 2023
Crystal structure of antibody bound to viral proteinCrystal structure of antibody bound to viral protein
Structural highlights
DiseasePSIP1_HUMAN Note=A chromosomal aberration involving PSIP1 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1/LEDGF exon 4. FunctionPSIP1_HUMAN Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.[1] Publication Abstract from PubMedPreventing the protein-protein interaction of the cellular chromatin binding protein Lens Epithelium-Derived Growth Factor (LEDGF) and human immunodeficiency virus (HIV) integrase is an important possible strategy for anti-viral treatment for AIDS. We have used Intracellular Antibody Capture technology to isolate a single VH antibody domain that binds to LEDGF. The crystal structure of the LEDGF-VH complex reveals that the single domain antibody mimics the effect of binding of HIV integrase to LEDGF which is crucial for HIV propagation. CD4-expressing T cell lines were constructed to constitutively express the LEDGF-binding VH and these cells showed interference with HIV viral replication, assayed by virus capsid protein p24 production. Therefore, pre-conditioning cells to express antibody fragments confers effective intracellular immunization for preventing chronic viral replication and can be a way to prevent HIV spread in infected patients. This raises the prospect that intracellular immunization strategies that focus on cellular components of viral integrase protein interactions can be used to combat the problems associated with latent HIV virus re-emergence in patients. New genome editing development, such as using CRISPR/cas9, offer the prospect intracellularly immunized T cells in HIV+ patients. Intracellular immunization against HIV infection with an intracellular antibody that mimics HIV integrase binding to the cellular LEDGF protein.,Bao L, Hannon C, Cruz-Mignoni A, Ptchelkine D, Sun MY, Miller A, Bunjobpol W, Quevedo CE, Derveni M, Chambers J, Simmons A, Phillips SEV, Rabbitts TH Sci Rep. 2017 Dec 4;7(1):16869. doi: 10.1038/s41598-017-16742-2. PMID:29203900[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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