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5ggv

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Revision as of 06:42, 13 May 2020

CTLA-4 in complex with tremelimumab Fab

Structural highlights

5ggv is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	5ggu, 5ggt, 5ggs, 5ggr, 5ggq
Gene:	CTLA4, CD152 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CTLA4_HUMAN] Genetic variation in CTLA4 influences susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. SLE is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. SLE is thought to represent a failure of the regulatory mechanisms of the autoimmune system.^[1] Note=Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism.^[2] Genetic variation in CTLA4 is the cause of susceptibility to diabetes mellitus insulin-dependent type 12 (IDDM12) [MIM:601388]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.^[3] ^[4] Genetic variation in CTLA4 is the cause of susceptibility to celiac disease type 3 (CELIAC3) [MIM:609755]. It is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins. In its classic form, celiac disease is characterized in children by malabsorption and failure to thrive.

Function

[CTLA4_HUMAN] Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28.^[5] ^[6]

Publication Abstract from PubMed

Cancer cells express tumour-specific antigens derived via genetic and epigenetic alterations, which may be targeted by T-cell-mediated immune responses. However, cancer cells can avoid immune surveillance by suppressing immunity through activation of specific inhibitory signalling pathways, referred to as immune checkpoints. In recent years, the blockade of checkpoint molecules such as PD-1, PD-L1 and CTLA-4, with monoclonal antibodies has enabled the development of breakthrough therapies in oncology, and four therapeutic antibodies targeting these checkpoint molecules have been approved by the FDA for the treatment of several types of cancer. Here, we report the crystal structures of checkpoint molecules in complex with the Fab fragments of therapeutic antibodies, including PD-1/pembrolizumab, PD-1/nivolumab, PD-L1/BMS-936559 and CTLA-4/tremelimumab. These complex structures elucidate the precise epitopes of the antibodies and the molecular mechanisms underlying checkpoint blockade, providing useful information for the improvement of monoclonal antibodies capable of attenuating checkpoint signalling for the treatment of cancer.

Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy.,Lee JY, Lee HT, Shin W, Chae J, Choi J, Kim SH, Lim H, Won Heo T, Park KY, Lee YJ, Ryu SE, Son JY, Lee JU, Heo YS Nat Commun. 2016 Oct 31;7:13354. doi: 10.1038/ncomms13354. PMID:27796306^[7]

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

References

↑ Chistyakov DA, Savost'anov KV, Turakulov RI, Petunina NA, Trukhina LV, Kudinova AV, Balabolkin MI, Nosikov VV. Complex association analysis of graves disease using a set of polymorphic markers. Mol Genet Metab. 2000 Jul;70(3):214-8. PMID:10924276 doi:10.1006/mgme.2000.3007
↑ Chistyakov DA, Savost'anov KV, Turakulov RI, Petunina NA, Trukhina LV, Kudinova AV, Balabolkin MI, Nosikov VV. Complex association analysis of graves disease using a set of polymorphic markers. Mol Genet Metab. 2000 Jul;70(3):214-8. PMID:10924276 doi:10.1006/mgme.2000.3007
↑ Chistyakov DA, Savost'anov KV, Turakulov RI, Petunina NA, Trukhina LV, Kudinova AV, Balabolkin MI, Nosikov VV. Complex association analysis of graves disease using a set of polymorphic markers. Mol Genet Metab. 2000 Jul;70(3):214-8. PMID:10924276 doi:10.1006/mgme.2000.3007
↑ Marron MP, Raffel LJ, Garchon HJ, Jacob CO, Serrano-Rios M, Martinez Larrad MT, Teng WP, Park Y, Zhang ZX, Goldstein DR, Tao YW, Beaurain G, Bach JF, Huang HS, Luo DF, Zeidler A, Rotter JI, Yang MC, Modilevsky T, Maclaren NK, She JX. Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups. Hum Mol Genet. 1997 Aug;6(8):1275-82. PMID:9259273
↑ Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991 Sep 1;174(3):561-9. PMID:1714933
↑ Teft WA, Kirchhof MG, Madrenas J. A molecular perspective of CTLA-4 function. Annu Rev Immunol. 2006;24:65-97. PMID:16551244 doi:10.1146/annurev.immunol.24.021605.090535
↑ Lee JY, Lee HT, Shin W, Chae J, Choi J, Kim SH, Lim H, Won Heo T, Park KY, Lee YJ, Ryu SE, Son JY, Lee JU, Heo YS. Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy. Nat Commun. 2016 Oct 31;7:13354. doi: 10.1038/ncomms13354. PMID:27796306 doi:http://dx.doi.org/10.1038/ncomms13354

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ggv"

Categories: Human | Large Structures | Heo, Y S | Antibody | Immune system

@@ Line 1: / Line 1: @@
 ==CTLA-4 in complex with tremelimumab Fab==
-<StructureSection load='5ggv' size='340' side='right' caption='[[5ggv]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='5ggv' size='340' side='right'caption='[[5ggv]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ggv]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GGV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GGV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ggv]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GGV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5GGV FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ggu|5ggu]], [[5ggt|5ggt]], [[5ggs|5ggs]], [[5ggr|5ggr]], [[5ggq|5ggq]]</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=5ggv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ggv OCA], [http://pdbe.org/5ggv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ggv RCSB], [http://www.ebi.ac.uk/pdbsum/5ggv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ggv ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTLA4, CD152 ([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'>[http://proteopedia.org/fgij/fg.htm?mol=5ggv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ggv OCA], [http://pdbe.org/5ggv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ggv RCSB], [http://www.ebi.ac.uk/pdbsum/5ggv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ggv ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Heo, Y S]]
 [[Category: Antibody]]
 [[Category: Immune system]]

5ggv

From Proteopedia

Revision as of 06:42, 13 May 2020

CTLA-4 in complex with tremelimumab Fab

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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