Alice Clark/BRCT

From Proteopedia

MCR1

Melanocortin 1 Receptor: An insight to MCR1 structure, function and regulation

Introduction to MC1R

The highly polymorphic human MC1R gene, located on chromosome 16q24.3 encodes for a MCR1 receptor also known as melanocyte -stimulating hormone receptor. The melanocortin receptor family consists of five members: MC1R, MCR2, MCR3, MC4R and MC5R all of which exhibit functions and are expressed differently (Wolf Horrell, Boulanger and D’Orazio, 2016). The gene is expressed in melanocytes along with other cell types that inhabit the skin such as keratinocytes and fibroblast as well as cells that operate the immune system (Gruis and Doorn, 2012). The activation of the MC1R receptor by ultraviolet radiation increases the production of the dark eumelanin pigment, resulting in the darkening of the skin. MCR1 stimulation also results in increased melanocyte dendricity, proliferation, cell survival and DNA repair. The loss of melanocortin receptor function results in the production of the red/yellow pheomelanin pigment by melanocytes, resulting in the red hair, fair skin, poor tanning, freckling and increased skin cancer risk in humans (Beaumont et al., 2011).

Determination of MC1R Structure

The mature MC1R protein is made up of 317 amino acids and a 7 a-helical transmembrane domain. Based on the sequence similarity analysis, the melanocortin receptor family belong to the class A of G-coupled protein receptors therefore direct information on their secondary and tertiary structures is limited as G coupled protein receptors are resistant to crystallisation (Garcia-Borron, Sanchez-Laorden and Jimenez-Cervantes, 2005) (Zhao and Wu, 2012).

MC4R Ligands

3D structures of MC4R

Updated on 27-January-2022

6w25 – hMC4R + peptide – human
7aue, 7f55, 7f58 – hMC4R in Gs protein complex + nanobody – Cryo EM
7piu – hMC4R in Gs protein complex + nanobody + drug – Cryo EM
7f53, 7piu, 7piv – hMC4R in Gs protein complex + nanobody + a-melanocyte-stimulating hormone – Cryo EM

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