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doi: 10.3389/fbioe.2021.677576 Received 07 March 2021 Accepted 12 April 2021 Published 29 April 2021 Volume 9 - 2021 Edited by Zhen Li, AO Research Institute, Switzerland Reviewed by Guangli Suo, Suzhou Institute of Nano-tech and Nano-bionics (CAS), China

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From Figures 3, 4, it is quite clear that there is a cluster of three charged residues, i.e., Arg123 (L23B R in Figure 2, B Leu 32 in 4ZGM [29, 52]) of semaglutides backbone, Arg127 (Arg36 in Figure 1, B ARG 36 in 4ZGM [29, 52]) of semaglutides backbone and Glu40 of GLP-1R ECD (A GLU 68 in 4ZGM [29, 52]), sitting at the binding interface of the semaglutide-GLP-1R complex structure (Figure 3 and 4)