6fax

From Proteopedia

(Difference between revisions)

Revision as of 06:58, 4 April 2018

Complex of Human CD40 Ectodomain with Lob 7.4 Fab

Structural highlights

6fax 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.
Gene:	CD40, TNFRSF5 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TNR5_HUMAN] Defects in CD40 are the cause of immunodeficiency with hyper-IgM type 3 (HIGM3) [MIM:606843]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.^[1]

Function

[TNR5_HUMAN] Receptor for TNFSF5/CD40LG.

Publication Abstract from PubMed

Anti-CD40 monoclonal antibodies (mAbs) that promote or inhibit receptor function hold promise as therapeutics for cancer and autoimmunity. Rules governing their diverse range of functions, however, are lacking. Here we determined characteristics of nine hCD40 mAbs engaging epitopes throughout the CD40 extracellular region expressed as varying isotypes. All mAb formats were strong agonists when hyper-crosslinked; however, only those binding the membrane-distal cysteine-rich domain 1 (CRD1) retained agonistic activity with physiological Fc gamma receptor crosslinking or as human immunoglobulin G2 isotype; agonistic activity decreased as epitopes drew closer to the membrane. In addition, all CRD2-4 binding mAbs blocked CD40 ligand interaction and were potent antagonists. Thus, the membrane distal CRD1 provides a region of choice for selecting CD40 agonists while CRD2-4 provides antagonistic epitopes.

Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies.,Yu X, Chan HTC, Orr CM, Dadas O, Booth SG, Dahal LN, Penfold CA, O'Brien L, Mockridge CI, French RR, Duriez P, Douglas LR, Pearson AR, Cragg MS, Tews I, Glennie MJ, White AL Cancer Cell. 2018 Mar 3. pii: S1535-6108(18)30062-X. doi:, 10.1016/j.ccell.2018.02.009. PMID:29576376^[2]

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

References

↑ Ferrari S, Giliani S, Insalaco A, Al-Ghonaium A, Soresina AR, Loubser M, Avanzini MA, Marconi M, Badolato R, Ugazio AG, Levy Y, Catalan N, Durandy A, Tbakhi A, Notarangelo LD, Plebani A. Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM. Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12614-9. PMID:11675497 doi:10.1073/pnas.221456898
↑ Yu X, Chan HTC, Orr CM, Dadas O, Booth SG, Dahal LN, Penfold CA, O'Brien L, Mockridge CI, French RR, Duriez P, Douglas LR, Pearson AR, Cragg MS, Tews I, Glennie MJ, White AL. Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies. Cancer Cell. 2018 Mar 3. pii: S1535-6108(18)30062-X. doi:, 10.1016/j.ccell.2018.02.009. PMID:29576376 doi:http://dx.doi.org/10.1016/j.ccell.2018.02.009

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/6fax"

@@ Line 3: / Line 3: @@
 <StructureSection load='6fax' size='340' side='right' caption='[[6fax]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6fax]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FAX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FAX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6fax]] 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=6FAX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FAX FirstGlance]. <br>
-</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=6fax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fax OCA], [http://pdbe.org/6fax PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fax RCSB], [http://www.ebi.ac.uk/pdbsum/6fax PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fax ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD40, TNFRSF5 ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fax OCA], [http://pdbe.org/6fax PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fax RCSB], [http://www.ebi.ac.uk/pdbsum/6fax PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fax ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 10: / Line 11: @@
 == Function ==
 [[http://www.uniprot.org/uniprot/TNR5_HUMAN TNR5_HUMAN]] Receptor for TNFSF5/CD40LG.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Anti-CD40 monoclonal antibodies (mAbs) that promote or inhibit receptor function hold promise as therapeutics for cancer and autoimmunity. Rules governing their diverse range of functions, however, are lacking. Here we determined characteristics of nine hCD40 mAbs engaging epitopes throughout the CD40 extracellular region expressed as varying isotypes. All mAb formats were strong agonists when hyper-crosslinked; however, only those binding the membrane-distal cysteine-rich domain 1 (CRD1) retained agonistic activity with physiological Fc gamma receptor crosslinking or as human immunoglobulin G2 isotype; agonistic activity decreased as epitopes drew closer to the membrane. In addition, all CRD2-4 binding mAbs blocked CD40 ligand interaction and were potent antagonists. Thus, the membrane distal CRD1 provides a region of choice for selecting CD40 agonists while CRD2-4 provides antagonistic epitopes.
+Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies.,Yu X, Chan HTC, Orr CM, Dadas O, Booth SG, Dahal LN, Penfold CA, O'Brien L, Mockridge CI, French RR, Duriez P, Douglas LR, Pearson AR, Cragg MS, Tews I, Glennie MJ, White AL Cancer Cell. 2018 Mar 3. pii: S1535-6108(18)30062-X. doi:, 10.1016/j.ccell.2018.02.009. PMID:29576376<ref>PMID:29576376</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6fax" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Orr, C M]]
 [[Category: Pearson, A R]]

6fax

From Proteopedia

Revision as of 06:58, 4 April 2018

Complex of Human CD40 Ectodomain with Lob 7.4 Fab

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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