|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6umg' size='340' side='right'caption='[[6umg]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='6umg' size='340' side='right'caption='[[6umg]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6umg]] is a 8 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=6UMG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UMG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6umg]] is a 8 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=6UMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UMG FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6umh|6umh]], [[6umi|6umi]], [[6umj|6umj]]</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]] 2.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CALCRL, CGRPR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RAMP1 ([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=6umg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6umg OCA], [https://pdbe.org/6umg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6umg RCSB], [https://www.ebi.ac.uk/pdbsum/6umg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6umg 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=6umg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6umg OCA], [http://pdbe.org/6umg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6umg RCSB], [http://www.ebi.ac.uk/pdbsum/6umg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6umg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RAMP1_HUMAN RAMP1_HUMAN]] Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for calcitonin-gene-related peptide (CGRP) together with CALCRL.<ref>PMID:9620797</ref> [[http://www.uniprot.org/uniprot/CALRL_HUMAN CALRL_HUMAN]] Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.<ref>PMID:22102369</ref> | + | [https://www.uniprot.org/uniprot/CALRL_HUMAN CALRL_HUMAN] Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.<ref>PMID:22102369</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 19: |
Line 18: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6umg" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6umg" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mohr, C]] | + | [[Category: Mohr C]] |
| - | [[Category: Class b gpcr]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Fragment antigen binding]]
| + | |
| - | [[Category: Membrane protein-immune system complex]]
| + | |
| Structural highlights
Function
CALRL_HUMAN Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.[1]
Publication Abstract from PubMed
Calcitonin-gene-related peptide (CGRP) plays a key role in migraine pathophysiology. Aimovig (erenumab; erenumab-aooe in the United States) is the only US Food and Drug Administration (FDA)-approved monoclonal antibody (mAb) therapy against the CGRP receptor (CGRPR) for the prevention of migraine. Aimovig is also the first FDA-approved mAb against a G-protein-coupled receptor (GPCR). Here, we report the architecture and functional attributes of erenumab critical for its potent antagonism against CGRPR. The crystal structure of erenumab in complex with CGRPR reveals a direct ligand-blocking mechanism, enabled by a remarkable 21-residue-long complementary determining region (CDR)-H3 loop, which adopts a tyrosine-rich helix-turn tip and projects into the deep interface of the calcitonin receptor-like receptor (CLR) and RAMP1 subunits of CGRPR. Furthermore, erenumab engages with residues specific to CLR and RAMP1, providing the molecular basis for its exquisite selectivity. Such structural insights reveal the drug action mechanism of erenumab and shed light on developing antibody therapeutics targeting GPCRs.
Molecular Insight into Recognition of the CGRPR Complex by Migraine Prevention Therapy Aimovig (Erenumab).,Garces F, Mohr C, Zhang L, Huang CS, Chen Q, King C, Xu C, Wang Z Cell Rep. 2020 Feb 11;30(6):1714-1723.e6. doi: 10.1016/j.celrep.2020.01.029. PMID:32049005[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kusano S, Kukimoto-Niino M, Hino N, Ohsawa N, Okuda K, Sakamoto K, Shirouzu M, Shindo T, Yokoyama S. Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Protein Sci. 2012 Feb;21(2):199-210. doi: 10.1002/pro.2003. Epub 2011 Dec 28. PMID:22102369 doi:10.1002/pro.2003
- ↑ Garces F, Mohr C, Zhang L, Huang CS, Chen Q, King C, Xu C, Wang Z. Molecular Insight into Recognition of the CGRPR Complex by Migraine Prevention Therapy Aimovig (Erenumab). Cell Rep. 2020 Feb 11;30(6):1714-1723.e6. doi: 10.1016/j.celrep.2020.01.029. PMID:32049005 doi:http://dx.doi.org/10.1016/j.celrep.2020.01.029
|
