3eo1: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
No edit summary
No edit summary
 
(3 intermediate revisions by the same user not shown)
Line 1: Line 1:
==Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3==
==Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3==
<StructureSection load='3eo1' size='340' side='right' caption='[[3eo1]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
<StructureSection load='3eo1' size='340' side='right'caption='[[3eo1]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3eo1]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EO1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EO1 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3eo1]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EO1 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3eo0|3eo0]]</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TGFB3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3eo1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eo1 OCA], [https://pdbe.org/3eo1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eo1 RCSB], [https://www.ebi.ac.uk/pdbsum/3eo1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eo1 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3eo1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eo1 OCA], [http://pdbe.org/3eo1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3eo1 RCSB], [http://www.ebi.ac.uk/pdbsum/3eo1 PDBsum]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/TGFB3_HUMAN TGFB3_HUMAN]] Defects in TGFB3 are a cause of familial arrhythmogenic right ventricular dysplasia type 1 (ARVD1) [MIM:[http://omim.org/entry/107970 107970]]; also known as arrhythmogenic right ventricular cardiomyopathy 1 (ARVC1). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall.<ref>PMID:15639475</ref> 
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/TGFB3_HUMAN TGFB3_HUMAN]] Involved in embryogenesis and cell differentiation.
[https://www.uniprot.org/uniprot/IGHG4_HUMAN IGHG4_HUMAN]  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eo/3eo1_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eo/3eo1_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
Line 32: Line 30:


==See Also==
==See Also==
*[[Antibody|Antibody]]
*[[Antibody 3D structures|Antibody 3D structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Lk3 transgenic mice]]
[[Category: Large Structures]]
[[Category: Gruetter, C]]
[[Category: Mus musculus]]
[[Category: Gruetter, M G]]
[[Category: Gruetter C]]
[[Category: Antibody-cytokine complex]]
[[Category: Gruetter MG]]
[[Category: Cardiomyopathy]]
[[Category: Cleavage on pair of basic residue]]
[[Category: Fab fragment]]
[[Category: Glycoprotein]]
[[Category: Growth factor]]
[[Category: Immune system-cytokine complex]]
[[Category: Mitogen]]
[[Category: Secreted]]

Latest revision as of 10:56, 9 October 2024

Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3

Structural highlights

3eo1 is a 12 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.1Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IGHG4_HUMAN

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

TGF-beta isoforms are key modulators of a broad range of biological pathways and increasingly are exploited as therapeutic targets. Here, we describe the crystal structures of a pan-TGF-beta neutralizing antibody, GC-1008, alone and in complex with TGF-beta3. The antibody is currently in clinical evaluation for idiopathic pulmonary fibrosis, melanoma, and renal cell cancer. GC-1008 recognizes an asymmetric binding interface across the TGF-beta homodimer with high affinity. Whereas both cognate receptors, TGF-beta-receptor types I and II, are required to recognize all 3 TGF-beta isoforms, GC-1008 has been engineered to bind with high affinity to TGF-beta1, 2, and 3 via a single interaction surface. Comparison with existing structures and models of TGF-beta interaction with its receptors suggests that the antibody binds to a similar epitope to the 2 receptors together and is therefore a structurally different but functionally identical mimic of the binding mode of both receptors.

A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions.,Grutter C, Wilkinson T, Turner R, Podichetty S, Finch D, McCourt M, Loning S, Jermutus L, Grutter MG Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20251-6. Epub 2008 Dec 10. PMID:19073914[1]

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

See Also

References

  1. Grutter C, Wilkinson T, Turner R, Podichetty S, Finch D, McCourt M, Loning S, Jermutus L, Grutter MG. A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions. Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20251-6. Epub 2008 Dec 10. PMID:19073914 doi:0807200106

3eo1, resolution 3.10Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA