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. 2019 Jul 31;10:515. doi: 10.3389/fendo.2019.00515

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Copyright © 2019 Heyder, Kleinau, Szczepek, Kwiatkowski, Speck, Soletto, Cerdá-Reverter, Krude, Kühnen, Biebermann and Scheerer.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Different putative MC4R homodimer and heteromer arrangements. The MC4R has the capacity to constitute homodimers or homo-oligomers (42–44). In (A,B), two different homodimeric MC4R constellations are supposed with different interfaces. (A) MC4R homodimer with an interface between parts of TMH4 (or H4), intracellular loop 2 (ICL2 or I2), and the TMH5 (or H5) based on the determined dimeric crystal structure of CXCR4 (cyan). Such arrangements should also be assumed for a heterodimeric constellation as reported for MC4R and MC3R (40) (gray, MC4R; green, MC3R). In (B), the MC4R protomers are in contact via the interface between TMH1-TMH2-H8 based on a determined KOR structure (magenta backbone). Heteromeric MC4R constellations, such as with the GPR7 (47), may also be arranged in such a constellation. Moreover, in (C) a tetrameric MC4R arrangement is shown, with the supposed interfaces alternating between dimers. (D) An alternating dimer arrangement for higher complexes is also feasible for tetrameric heteromers.