9LKM

Focused map of C1ql1-gC1q trimer and BAI3-eCUB complex

Summary for 9LKM

• Entry DOI: 10.2210/pdb9lkm/pdb
• EMDB information: 63182
• Descriptor: C1q-related factor, Adhesion G protein-coupled receptor B3, CALCIUM ION (3 entities in total)
• Functional Keywords: c1ql1, bai3, synapse, cf-pc, calcium, signaling protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 5
• Total formula weight: 88390.17

Authors

Liao, L.,Niu, F.,Wei, Z. (deposition date: 2025-01-16, release date: 2025-12-17)

Primary citation

Liao, L.,Han, Y.,Niu, F.,Wang, Y.,Lu, Y.,Xu, S.,Zhu, H.,Lin, L.,Xiao, J.,Tou, H.I.,Gao, J.,Zhang, B.,Wei, Z.
Structural basis of calcium-dependent C1ql1/BAI3 assemblies in synaptic connectivity.
Nat Commun, 2025

PubMed Abstract: Cell adhesion molecules (CAMs) are pivotal in establishing and maintaining synaptic connectivity. Emerging evidence indicates that some secreted factors within the synaptic cleft, including C1q-like proteins (C1qls), play a crucial role in bridging pre- and post-synapses by connecting the bilateral CAMs. However, the mechanisms of those secreted factors in synapse assembly remain incomplete. Here, we explore C1ql-mediated synaptic connectivity, focusing on the assembly of C1ql1 and its postsynaptic receptor brain-specific angiogenesis inhibitor 3 (BAI3, also called ADGRB3). Our biochemical, structural, and computational analyses reveal that the trimeric globular C1q (gC1q) domain of C1ql1 undergoes a calcium-modulated domain-swapping event to form a hexamer. Cryo-EM study manifests the stabilizing role of calcium ions on the C1ql1_gC1q hexamer in complex with the extended CUB domain of BAI3. Using the gC1q hexamer, full-length C1ql1 further assembles into linear clusters, possibly providing a scaffold to accumulate BAI3 receptors on the plasma membrane. Our cellular and in vivo studies support a role for the gC1q-mediated dynamic assembly of C1ql1 in receptor accumulation and synapse maintenance. Collectively, our findings provide a plausible mechanism of secreted factor-mediated synaptic connectivity, driven by the calcium-modulated assembly of C1qls and their interactions with CAMs.

PubMed: 41372137
DOI: 10.1038/s41467-025-66254-1

Experimental method

ELECTRON MICROSCOPY (3.34 Å)