Structure Report for: 8GS4

Zhenzhen Zhang, Mengzhuo Hou, Huaxing Ou, Daping Wang, Zhifang Li, Huawei Zhang, Jianping Lu

Title: Expression and structural analysis of human neuroligin 2 and neuroligin 3 implicated in autism spectrum disorders
Zhang Z, Hou M, Ou H, Wang D, Li Z, Zhang H, Lu J
Ref: Front Endocrinol (Lausanne), 13:1067529, 2022 : PubMed
Abstract


ESTHER: Zhang_2022_Front.Endocrinol.(Lausanne)_13_1067529
PubMedSearch: Zhang 2022 Front.Endocrinol.(Lausanne) 13 1067529
PubMedID: 36479216
Gene_locus related to this paper: human-NLGN2, human-NLGN3

Abstract

The development of autism spectrum disorders (ASDs) involves both environmental factors such as maternal diabetes and genetic factors such as neuroligins (NLGNs). NLGN2 and NLGN3 are two members of NLGNs with distinct distributions and functions in synapse development and plasticity. The relationship between maternal diabetes and NLGNs, and the distinct working mechanisms of different NLGNs currently remain unclear. Here, we first analyzed the expression levels of NLGN2 and NLGN3 in a streptozotocin-induced ASD mouse model and different brain regions to reveal their differences and similarities. Then, cryogenic electron microscopy (cryo-EM) structures of human NLGN2 and NLGN3 were determined. The overall structures are similar to their homologs in previous reports. However, structural comparisons revealed the relative rotations of two protomers in the homodimers of NLGN2 and NLGN3. Taken together with the previously reported NLGN2-MDGA1 complex, we speculate that the distinct assembly adopted by NLGN2 and NLGN3 may affect their interactions with MDGAs. Our results provide structural insights into the potential distinct mechanisms of NLGN2 and NLGN3 implicated in the development of ASD.