G-protein coupled receptor family C group 5 member D is a protein that in humans is encoded by the GPRC5D gene.[5] GPRC5D is a class C orphan G protein-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.[6][7][8]
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. [9]
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.[5]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000111291 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030205 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "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, et al. (March 2019). "GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells". Science Translational Medicine. 11 (485). doi:10.1126/scitranslmed.aau7746. PMC 7508042. PMID 30918115.
- ^ Verkleij CP, Broekmans ME, van Duin M, Frerichs KA, Kuiper R, de Jonge AV, et al. (April 2021). "Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma". Blood Advances. 5 (8): 2196–2215. doi:10.1182/bloodadvances.2020003805. PMC 8095149. PMID 33890981.
- ^ 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. doi:10.1016/j.jmb.2024.168748. PMID 39181182.
Further reading
- Bräuner-Osborne H, Jensen AA, Sheppard PO, Brodin B, Krogsgaard-Larsen P, O'Hara P (April 2001). "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. doi:10.1016/s0167-4781(01)00197-x. PMID 11311935.
- Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S (June 2002). "Identification of G protein-coupled receptor genes from the human genome sequence". FEBS Letters. 520 (1–3): 97–101. Bibcode:2002FEBSL.520...97T. doi:10.1016/S0014-5793(02)02775-8. PMID 12044878. S2CID 7116392.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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