8xgo

From Proteopedia

(Difference between revisions)

Current revision

a peptide receptor complex structure

Structural highlights

8xgo is a 6 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.68Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

KISSR_HUMAN Genetic central precocious puberty in female;Normosmic congenital hypogonadotropic hypogonadism;Genetic central precocious puberty in male. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in KISS1R as well as in other HH-associated genes including FGFR1 and IL17RD (PubMed:23643382).^[1] The disease is caused by variants affecting the gene represented in this entry.

Function

KISSR_HUMAN Receptor for metastin (kisspeptin-54 or kp-54), a C-terminally amidated peptide of KiSS1. KiSS1 is a metastasis suppressor protein that suppresses metastases in malignant melanomas and in some breast carcinomas without affecting tumorigenicity. The metastasis suppressor properties may be mediated in part by cell cycle arrest and induction of apoptosis in malignant cells. The receptor is essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/KISS1R system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood. The receptor is also probably involved in the regulation and fine-tuning of trophoblast invasion generated by the trophoblast itself. Analysis of the transduction pathways activated by the receptor identifies coupling to phospholipase C and intracellular calcium release through pertussis toxin-insensitive G(q) proteins.^[2]

Publication Abstract from PubMed

Kisspeptin receptor (KISS1R), belonging to the class A peptide-GPCR family, plays a key role in the regulation of reproductive physiology after stimulation by kisspeptin and is regarded as an attractive drug target for reproductive diseases. Here, we demonstrated that KISS1R can couple to the G(i/o) pathway besides the well-known G(q/11) pathway. We further resolved the cryo-electron microscopy (cryo-EM) structure of KISS1R-G(q) and KISS1R-G(i) complexes bound to the synthetic agonist TAK448 and structure of KISS1R-G(q) complex bound to the endogenous agonist KP54. The high-resolution structures provided clear insights into mechanism of KISS1R recognition by its ligand and can facilitate the design of targeted drugs with high affinity to improve treatment effects. Moreover, the structural and functional analyses indicated that conformational differences in the extracellular loops (ECLs), intracellular loops (ICLs) of the receptor, and the "wavy hook" of the Galpha subunit may account for the specificity of G protein coupling for KISS1R signaling.

Structural basis for the ligand recognition and G protein subtype selectivity of kisspeptin receptor.,Wu Z, Chen G, Qiu C, Yan X, Xu L, Jiang S, Xu J, Han R, Shi T, Liu Y, Gao W, Wang Q, Li J, Ye F, Pan X, Zhang Z, Ning P, Zhang B, Chen J, Du Y Sci Adv. 2024 Aug 16;10(33):eadn7771. doi: 10.1126/sciadv.adn7771. Epub 2024 Aug , 16. PMID:39151001^[3]

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

References

↑ Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, Chanoine JP, Rubenstein J, Mohammadi M, Tsai PS, Sidis Y, Lage K, Pitteloud N. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008. PMID:23643382 doi:http://dx.doi.org/10.1016/j.ajhg.2013.04.008
↑ Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C, Malli R, Sharabi A, Hiden U, Graier W, Knöfler M, Andreae F, Wagner O, Quaranta V, Desoye G. Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci. 2004 Mar 15;117(Pt 8):1319-28. PMID:15020672 doi:10.1242/jcs.00971
↑ Wu Z, Chen G, Qiu C, Yan X, Xu L, Jiang S, Xu J, Han R, Shi T, Liu Y, Gao W, Wang Q, Li J, Ye F, Pan X, Zhang Z, Ning P, Zhang B, Chen J, Du Y. Structural basis for the ligand recognition and G protein subtype selectivity of kisspeptin receptor. Sci Adv. 2024 Aug 16;10(33):eadn7771. PMID:39151001 doi:10.1126/sciadv.adn7771

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/8xgo"

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[8xgo]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8XGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XGO FirstGlance]. <br>
 </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.68&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DTH:D-THREONINE'>DTH</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=NMM:(2S)-2-AMINO-5-[(N-METHYLCARBAMIMIDOYL)AMINO]PENTANOIC+ACID'>NMM</scene>, <scene name='pdbligand=UYA:(2~{R},4~{R})-4-oxidanylpyrrolidine-2-carboxylic+acid'>UYA</scene>, <scene name='pdbligand=XZA:diazanecarboxylic+acid'>XZA</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DTH:D-THREONINE'>DTH</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=NMM:(2S)-2-AMINO-5-[(N-METHYLCARBAMIMIDOYL)AMINO]PENTANOIC+ACID'>NMM</scene>, <scene name='pdbligand=UYA:(4R)-4-hydroxy-D-proline'>UYA</scene>, <scene name='pdbligand=XZA:diazanecarboxylic+acid'>XZA</scene></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=8xgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xgo OCA], [https://pdbe.org/8xgo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xgo RCSB], [https://www.ebi.ac.uk/pdbsum/8xgo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xgo ProSAT]</span></td></tr>
 </table>

8xgo

From Proteopedia

Current revision

a peptide receptor complex structure

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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