Cbln1 and Cbln4 Are Structurally Similar but Differ in GluD2 Binding Interactions

Publication date: 5 September 2017
Source:Cell Reports, Volume 20, Issue 10
Author(s): Chen Zhong, Jinlong Shen, Huibing Zhang, Guangyi Li, Senlin Shen, Fang Wang, Kuan Hu, Longxing Cao, Yongning He, Jianping Ding
SummaryUnlike cerebellin 1 (Cbln1), which bridges neurexin (Nrxn) receptors and δ-type glutamate receptors in a trans-synaptic triad, Cbln4 was reported to have no or weak binding for the receptors despite sharing ∼70% sequence identity with Cbln1. Here, we report crystal structures of the homotrimers of the C1q domain of Cbln1 and Cbln4 at 2.2 and 2.3 Å resolution, respectively. Comparison of the structures suggests that the difference between Cbln1 and Cbln4 in GluD2 binding might be because of their sequence and structural divergence in loop CD. Surprisingly, we show that Cbln4 binds to Nrxn1β and forms a stable complex with the laminin, nectin, sex-hormone binding globulin (LNS) domain of Nrxn1β. Furthermore, the negative-stain electron microscopy reconstruction of hexameric full-length Cbln1 at 13 Å resolution and that of the Cbln4/Nrxn1β complex at 19 Å resolution suggest that Nrxn1β binds to the N-terminal region of Cbln4, probably through strand β10 of the S4 insert.

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Teaser

Cbln1 and Cbln4 share high sequence identity but have divergent functions. Zhong et al. find that Cbln4 forms a complex with Nrxn1β. Using crystal structures of the C1q domain of Cbln1 and Cbln4 and negative-stain EM reconstructions of Cbln1 and Cbln4/Nrxn1β, the authors examine similarities and divergence between Cbln1 and Cbln4.


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