3u7y

From Proteopedia

(Difference between revisions)

Current revision

Structure of NIH45-46 Fab in complex with gp120 of 93TH057 HIV

Structural highlights

3u7y is a 3 chain structure with sequence from Homo sapiens and Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4478Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

IGHG1_HUMAN Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:254500. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.

Function

IGHG1_HUMAN

Publication Abstract from PubMed

Antibodies against the CD4 binding site (CD4bs) on the HIV-1 spike protein gp120 can show exceptional potency and breadth. We determined structures of NIH45-46, a more potent clonal variant of VRC01, alone and bound to gp120. Comparisons with VRC01-gp120 revealed that a four-residue insertion in CDRH3 contributed to increased interaction between NIH45-46 and the gp120 inner domain, which correlated with enhanced neutralization. We used structure-based design to create NIH45-46(G54W), a single substitution in CDRH2 that increases contact with the gp120 bridging sheet and improves breadth and potency, critical properties for potential clinical use, by an order of magnitude. Together with the NIH45-46-gp120 structure, these results indicate that gp120 inner domain/bridging sheet residues should be included in immunogens to elicit CD4bs antibodies.

Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design.,Diskin R, Scheid JF, Marcovecchio PM, West AP Jr, Klein F, Gao H, Gnanapragasam PN, Abadir A, Seaman MS, Nussenzweig MC, Bjorkman PJ Science. 2011 Oct 27. PMID:22033520^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Diskin R, Scheid JF, Marcovecchio PM, West AP Jr, Klein F, Gao H, Gnanapragasam PN, Abadir A, Seaman MS, Nussenzweig MC, Bjorkman PJ. Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design. Science. 2011 Oct 27. PMID:22033520 doi:10.1126/science.1213782

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3u7y"

Categories: Homo sapiens | Human immunodeficiency virus 1 | Large Structures | Bjorkman PJ | Diskin R

@@ Line 1: / Line 1: @@
-[[Image:3u7y.png|left|200px]]
-<!--
+==Structure of NIH45-46 Fab in complex with gp120 of 93TH057 HIV==
-The line below this paragraph, containing "STRUCTURE_3u7y", creates the "Structure Box" on the page.
+<StructureSection load='3u7y' size='340' side='right'caption='[[3u7y]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3u7y]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U7Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U7Y FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4478&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
-{{STRUCTURE_3u7y|  PDB=3u7y  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3u7y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u7y OCA], [https://pdbe.org/3u7y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u7y RCSB], [https://www.ebi.ac.uk/pdbsum/3u7y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u7y ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[https://omim.org/entry/254500 254500]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.
+== Function ==
+[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Antibodies against the CD4 binding site (CD4bs) on the HIV-1 spike protein gp120 can show exceptional potency and breadth. We determined structures of NIH45-46, a more potent clonal variant of VRC01, alone and bound to gp120. Comparisons with VRC01-gp120 revealed that a four-residue insertion in CDRH3 contributed to increased interaction between NIH45-46 and the gp120 inner domain, which correlated with enhanced neutralization. We used structure-based design to create NIH45-46(G54W), a single substitution in CDRH2 that increases contact with the gp120 bridging sheet and improves breadth and potency, critical properties for potential clinical use, by an order of magnitude. Together with the NIH45-46-gp120 structure, these results indicate that gp120 inner domain/bridging sheet residues should be included in immunogens to elicit CD4bs antibodies.
-===Structure of NIH45-46 Fab in complex with gp120 of 93TH057 HIV===
+Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design.,Diskin R, Scheid JF, Marcovecchio PM, West AP Jr, Klein F, Gao H, Gnanapragasam PN, Abadir A, Seaman MS, Nussenzweig MC, Bjorkman PJ Science. 2011 Oct 27. PMID:22033520<ref>PMID:22033520</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3u7y" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22033520}}, adds the Publication Abstract to the page
+*[[Gp120 3D structures|Gp120 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22033520 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22033520}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[3u7y]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U7Y OCA].
-==Reference==
-<ref group="xtra">PMID:022033520</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
 [[Category: Human immunodeficiency virus 1]]
-[[Category: Bjorkman, P J.]]
+[[Category: Large Structures]]
-[[Category: Diskin, R.]]
+[[Category: Bjorkman PJ]]
-[[Category: Anti hiv]]
+[[Category: Diskin R]]
-[[Category: Glycosylation]]
-[[Category: Gp120]]
-[[Category: Ig fold]]
-[[Category: Viral protein-immune system complex]]

3u7y

From Proteopedia

Current revision

Structure of NIH45-46 Fab in complex with gp120 of 93TH057 HIV

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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