6dkj

From Proteopedia

(Difference between revisions)

Current revision

human GIPR ECD and Fab complex

Structural highlights

6dkj is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.95Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IGG1_HUMAN Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:20176268, PubMed:17576170).^[1] ^[2] ^[3]

Publication Abstract from PubMed

Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) has been identified in multiple genome-wide association studies (GWAS) as a contributor to obesity, and GIPR knockout mice are protected against diet-induced obesity (DIO). On the basis of this genetic evidence, we developed anti-GIPR antagonistic antibodies as a potential therapeutic strategy for the treatment of obesity and observed that a mouse anti-murine GIPR antibody (muGIPR-Ab) protected against body weight gain, improved multiple metabolic parameters, and was associated with reduced food intake and resting respiratory exchange ratio (RER) in DIO mice. We replicated these results in obese nonhuman primates (NHPs) using an anti-human GIPR antibody (hGIPR-Ab) and found that weight loss was more pronounced than in mice. In addition, we observed enhanced weight loss in DIO mice and NHPs when anti-GIPR antibodies were codosed with glucagon-like peptide-1 receptor (GLP-1R) agonists. Mechanistic and crystallographic studies demonstrated that hGIPR-Ab displaced GIP and bound to GIPR using the same conserved hydrophobic residues as GIP. Further, using a conditional knockout mouse model, we excluded the role of GIPR in pancreatic beta-cells in the regulation of body weight and response to GIPR antagonism. In conclusion, these data provide preclinical validation of a therapeutic approach to treat obesity with anti-GIPR antibodies.

Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models.,Killion EA, Wang J, Yie J, Shi SD, Bates D, Min X, Komorowski R, Hager T, Deng L, Atangan L, Lu SC, Kurzeja RJM, Sivits G, Lin J, Chen Q, Wang Z, Thibault SA, Abbott CM, Meng T, Clavette B, Murawsky CM, Foltz IN, Rottman JB, Hale C, Veniant MM, Lloyd DJ Sci Transl Med. 2018 Dec 19;10(472). pii: 10/472/eaat3392. doi:, 10.1126/scitranslmed.aat3392. PMID:30567927^[4]

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

References

↑ Teng G, Papavasiliou FN. Immunoglobulin somatic hypermutation. Annu Rev Genet. 2007;41:107-20. PMID:17576170 doi:http://dx.doi.org/10.1146/annurev.genet.41.110306.130340
↑ Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S41-52. doi:, 10.1016/j.jaci.2009.09.046. PMID:20176268 doi:http://dx.doi.org/10.1016/j.jaci.2009.09.046
↑ McHeyzer-Williams M, Okitsu S, Wang N, McHeyzer-Williams L. Molecular programming of B cell memory. Nat Rev Immunol. 2011 Dec 9;12(1):24-34. doi: 10.1038/nri3128. PMID:22158414 doi:http://dx.doi.org/10.1038/nri3128
↑ Killion EA, Wang J, Yie J, Shi SD, Bates D, Min X, Komorowski R, Hager T, Deng L, Atangan L, Lu SC, Kurzeja RJM, Sivits G, Lin J, Chen Q, Wang Z, Thibault SA, Abbott CM, Meng T, Clavette B, Murawsky CM, Foltz IN, Rottman JB, Hale C, Veniant MM, Lloyd DJ. Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models. Sci Transl Med. 2018 Dec 19;10(472). pii: 10/472/eaat3392. doi:, 10.1126/scitranslmed.aat3392. PMID:30567927 doi:http://dx.doi.org/10.1126/scitranslmed.aat3392

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6dkj"

Categories: Homo sapiens | Large Structures | Min X | Wang Z

@@ Line 3: / Line 3: @@
 <StructureSection load='6dkj' size='340' side='right'caption='[[6dkj]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6dkj]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DKJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6dkj]] is a 6 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=6DKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DKJ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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]] 1.95&#8491;</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=6dkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dkj OCA], [http://pdbe.org/6dkj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dkj RCSB], [http://www.ebi.ac.uk/pdbsum/6dkj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dkj ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6dkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dkj OCA], [https://pdbe.org/6dkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dkj RCSB], [https://www.ebi.ac.uk/pdbsum/6dkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dkj ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GIPR_HUMAN GIPR_HUMAN]] This is a receptor for GIP. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
+[https://www.uniprot.org/uniprot/IGG1_HUMAN IGG1_HUMAN] Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:20176268, PubMed:17576170).<ref>PMID:17576170</ref> <ref>PMID:20176268</ref> <ref>PMID:22158414</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 6dkj" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
+*[[Glucose-dependent Insulinotropic Polypeptide Receptor|Glucose-dependent Insulinotropic Polypeptide Receptor]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Min, X]]
+[[Category: Min X]]
-[[Category: Wang, Z]]
+[[Category: Wang Z]]
-[[Category: Gpcr]]
-[[Category: Signaling protein]]

6dkj

From Proteopedia

Current revision

human GIPR ECD and Fab complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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