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. 2021 Apr 12;11:7858. doi: 10.1038/s41598-021-87251-6

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Red sectors are mediator between GPCR and G protein signaling. (a) Construction of new multiple sequence alignments for integrated analysis of GPCR-G protein. (b) Results of integrated SCA. Blurred matrices are original sector matrix of HTR and G protein. The cross section of each matrix is covariation between HTR sectors and G protein sectors. (c) Structure representation of HTR-Red and G-Red which have high coevolution signals. (d) Sequence logo and amino acids patterns of HTR-Red and G-Red interaction. In amino acid pattern figure, x, y axis represent the amino acid order of three letter code alphabetically from top to bottom, left to right. (one letter code order: ARNDCQEGHILKMFPSTWYV-, -represents gap). (e) Amino acid pattern analysis between HTR-Red and G-Red residues. Patterns of each color are explained in legend. Same shape in each column represents similar distribution of amino acids’ pair.