View source for 6wmw


==GFRAL receptor bound with two antibody Fabs (3P10, 25M22)==
<StructureSection load='6wmw' size='340' side='right'caption='[[6wmw]], [[Resolution|resolution]] 2.91&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wmw]] is a 5 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=6WMW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WMW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.91&#8491;</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=6wmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wmw OCA], [https://pdbe.org/6wmw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wmw RCSB], [https://www.ebi.ac.uk/pdbsum/6wmw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wmw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GFRAL_HUMAN GFRAL_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cancer cachexia is a highly prevalent condition associated with poor quality of life and reduced survival(1). Tumor-induced perturbations in the endocrine, immune and nervous systems drive anorexia and catabolic changes in adipose tissue and skeletal muscle, hallmarks of cancer cachexia(2-4). However, the molecular mechanisms driving cachexia remain poorly defined, and there are currently no approved drugs for the condition. Elevation in circulating growth differentiation factor 15 (GDF15) correlates with cachexia and reduced survival in patients with cancer(5-8), and a GDNF family receptor alpha like (GFRAL)-Ret proto-oncogene (RET) signaling complex in brainstem neurons that mediates GDF15-induced weight loss in mice has recently been described(9-12). Here we report a therapeutic antagonistic monoclonal antibody, 3P10, that targets GFRAL and inhibits RET signaling by preventing the GDF15-driven interaction of RET with GFRAL on the cell surface. Treatment with 3P10 reverses excessive lipid oxidation in tumor-bearing mice and prevents cancer cachexia, even under calorie-restricted conditions. Mechanistically, activation of the GFRAL-RET pathway induces expression of genes involved in lipid metabolism in adipose tissues, and both peripheral chemical sympathectomy and loss of adipose triglyceride lipase protect mice from GDF15-induced weight loss. These data uncover a peripheral sympathetic axis by which GDF15 elicits a lipolytic response in adipose tissue independently of anorexia, leading to reduced adipose and muscle mass and function in tumor-bearing mice.

Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice.,Suriben R, Chen M, Higbee J, Oeffinger J, Ventura R, Li B, Mondal K, Gao Z, Ayupova D, Taskar P, Li D, Starck SR, Chen HH, McEntee M, Katewa SD, Phung V, Wang M, Kekatpure A, Lakshminarasimhan D, White A, Olland A, Haldankar R, Solloway MJ, Hsu JY, Wang Y, Tang J, Lindhout DA, Allan BB Nat Med. 2020 Aug;26(8):1264-1270. doi: 10.1038/s41591-020-0945-x. Epub 2020 Jul , 13. PMID:32661391<ref>PMID:32661391</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wmw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lakshminarasimhan D]]
[[Category: Olland A]]
[[Category: Suto RK]]
[[Category: White A]]