GPRC5D explained
G-protein coupled receptor family C group 5 member D is a protein that in humans is encoded by the GPRC5D gene.[1] GPRC5D is a class C orphan Gprotein-coupled receptor predominantly expressed in multiple myeloma cells and hard keratinized tissues, with low expression in normal human tissues, rendering it an appealing target for multiple myeloma cells.[2] [3] [4]
Structure
Structural analysis of the complex between GPRC5D and Talquetamab, a bispecific antibody for the treatment of multiple myeloma, has revealed that GPRC5D exists as a dimer. GPRC5D forms a symmetric dimer via TM4 and TM4/TM5 interactions. The study further demonstrated that only one Talquetamab molecule can bind to the dimeric form of GPRC5D. Talquetamab Fab recognizes ECLs and TM3/5/7 of one GPRC5D protomer via six CDRs. [5]
Function
The protein encoded by this gene is a member of the G protein-coupled receptor family; however, the specific function of this gene has not yet been determined.
See also
Further reading
- Bräuner-Osborne H, Jensen AA, Sheppard PO, Brodin B, Krogsgaard-Larsen P, O'Hara P . Cloning and characterization of a human orphan family C G-protein coupled receptor GPRC5D . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1518 . 3 . 237–248 . April 2001 . 11311935 . 10.1016/s0167-4781(01)00197-x .
- Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S . Identification of G protein-coupled receptor genes from the human genome sequence . FEBS Letters . 520 . 1–3 . 97–101 . June 2002 . 12044878 . 10.1016/S0014-5793(02)02775-8 . 7116392 . 2002FEBSL.520...97T .
Notes and References
- Web site: Entrez Gene: GPRC5D G protein-coupled receptor, family C, group 5, member D.
- The RAIG family member, GPRC5D, is associated with hard-keratinized structures . J. Invest. Dermatol. .
- Smith EL, Harrington K, Staehr M, Masakayan R, Jones J, Long TJ, Ng KY, Ghoddusi M, Purdon TJ, Wang X, Do T, Pham MT, Brown JM, De Larrea CF, Olson E, Peguero E, Wang P, Liu H, Xu Y, Garrett-Thomson SC, Almo SC, Wendel HG, Riviere I, Liu C, Sather B, Brentjens RJ . GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells . Science Translational Medicine . 11 . 485 . March 2019 . 30918115 . 7508042 . 10.1126/scitranslmed.aau7746 .
- Verkleij CP, Broekmans ME, van Duin M, Frerichs KA, Kuiper R, de Jonge AV, Kaiser M, Morgan G, Axel A, Boominathan R, Sendecki J, Wong A, Verona RI, Sonneveld P, Zweegman S, Adams HC, Mutis T, van de Donk NW . Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma . Blood Advances . 5 . 8 . 2196–2215 . April 2021 . 33890981 . 8095149 . 10.1182/bloodadvances.2020003805 .
- Jeong J, Park J, Young Mo G, Shin J, Cho Y . August 2024 . Structural Basis for the Recognition of GPRC5D by Talquetamab, a Bispecific Antibody for Multiple Myeloma . Journal of Molecular Biology . 436 . 20 . 168748 . 10.1016/j.jmb.2024.168748 . 39181182.
