6yxd

Room temperature structure of human adiponectin receptor 2 (ADIPOR2) at 2.9 A resolution determined by Serial Crystallography (SSX) using CrystalDirect

Structural highlights

6yxd is a 3 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 2.9Å
Ligands:	GOL, OLA, OLB, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PAQR2_HUMAN Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism (PubMed:12802337, PubMed:25855295). Required for normal body fat and glucose homeostasis. ADIPOQ-binding activates a signaling cascade that leads to increased PPARA activity, and ultimately to increased fatty acid oxidation and glucose uptake. Has intermediate affinity for globular and full-length adiponectin. Required for normal revascularization after chronic ischemia caused by severing of blood vessels (By similarity).[UniProtKB:Q8BQS5]^[1] ^[2]

Publication Abstract from PubMed

Membrane proteins are central to many pathophysiological processes, yet remain very difficult to analyze structurally. Moreover, high-throughput structure-based drug discovery has not yet been exploited for membrane proteins because of lack of automation. Here, we present a facile and versatile platform for in meso membrane protein crystallization, enabling rapid atomic structure determination at both cryogenic and room temperatures. We apply this approach to human integral membrane proteins, which allowed us to identify different conformational states of intramembrane enzyme-product complexes and analyze by molecular dynamics simulations the structural dynamics of the ADIPOR2 integral membrane protein. Finally, we demonstrate an automated pipeline combining high-throughput microcrystal soaking, automated laser-based harvesting, and serial crystallography, enabling screening of small-molecule libraries with membrane protein crystals grown in meso. This approach brings needed automation to this important class of drug targets and enables high-throughput structure-based ligand discovery with membrane proteins.

An automated platform for structural analysis of membrane proteins through serial crystallography.,Healey RD, Basu S, Humm AS, Leyrat C, Cong X, Golebiowski J, Dupeux F, Pica A, Granier S, Marquez JA Cell Rep Methods. 2021 Oct 25;1(6):None. doi: 10.1016/j.crmeth.2021.100102. PMID:34723237^[3]

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

References

↑ Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003 Jun 12;423(6941):762-9. PMID:12802337 doi:https://dx.doi.org/10.1038/nature01705
↑ Tanabe H, Fujii Y, Okada-Iwabu M, Iwabu M, Nakamura Y, Hosaka T, Motoyama K, Ikeda M, Wakiyama M, Terada T, Ohsawa N, Hato M, Ogasawara S, Hino T, Murata T, Iwata S, Hirata K, Kawano Y, Yamamoto M, Kimura-Someya T, Shirouzu M, Yamauchi T, Kadowaki T, Yokoyama S. Crystal structures of the human adiponectin receptors. Nature. 2015 Apr 16;520(7547):312-6. doi: 10.1038/nature14301. Epub 2015 Apr 8. PMID:25855295 doi:https://dx.doi.org/10.1038/nature14301
↑ Healey RD, Basu S, Humm AS, Leyrat C, Cong X, Golebiowski J, Dupeux F, Pica A, Granier S, Marquez JA. An automated platform for structural analysis of membrane proteins through serial crystallography. Cell Rep Methods. 2021 Oct 25;1(6):None. doi: 10.1016/j.crmeth.2021.100102. PMID:34723237 doi:https://dx.doi.org/10.1016/j.crmeth.2021.100102

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OCA

[1] Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003 Jun 12;423(6941):762-9. PMID:12802337 doi:https://dx.doi.org/10.1038/nature01705

[2] Tanabe H, Fujii Y, Okada-Iwabu M, Iwabu M, Nakamura Y, Hosaka T, Motoyama K, Ikeda M, Wakiyama M, Terada T, Ohsawa N, Hato M, Ogasawara S, Hino T, Murata T, Iwata S, Hirata K, Kawano Y, Yamamoto M, Kimura-Someya T, Shirouzu M, Yamauchi T, Kadowaki T, Yokoyama S. Crystal structures of the human adiponectin receptors. Nature. 2015 Apr 16;520(7547):312-6. doi: 10.1038/nature14301. Epub 2015 Apr 8. PMID:25855295 doi:https://dx.doi.org/10.1038/nature14301

[3] Healey RD, Basu S, Humm AS, Leyrat C, Cong X, Golebiowski J, Dupeux F, Pica A, Granier S, Marquez JA. An automated platform for structural analysis of membrane proteins through serial crystallography. Cell Rep Methods. 2021 Oct 25;1(6):None. doi: 10.1016/j.crmeth.2021.100102. PMID:34723237 doi:https://dx.doi.org/10.1016/j.crmeth.2021.100102

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6yxd

Room temperature structure of human adiponectin receptor 2 (ADIPOR2) at 2.9 A resolution determined by Serial Crystallography (SSX) using CrystalDirect

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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