3M45

Crystal structure of Ig1 domain of mouse SynCAM 2

Summary for 3M45

• Entry DOI: 10.2210/pdb3m45/pdb
• Descriptor: Cell adhesion molecule 2, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: ig fold, dimer, disulfide bond, glycoprotein, immunoglobulin domain, membrane, transmembrane, cell adhesion
• Biological source: Mus musculus (mouse)
• Cellular location: Membrane; Single-pass type I membrane protein (Potential): Q8BLQ9
• Total number of polymer chains: 4
• Total formula weight: 49289.87

Authors

Yue, L.,Modis, Y. (deposition date: 2010-03-10, release date: 2010-09-08, Last modification date: 2024-11-06)

Primary citation

Fogel, A.I.,Li, Y.,Giza, J.,Wang, Q.,Lam, T.T.,Modis, Y.,Biederer, T.
N-glycosylation at the SynCAM (synaptic cell adhesion molecule) immunoglobulin interface modulates synaptic adhesion.
J.Biol.Chem., 285:34864-34874, 2010

PubMed Abstract: Select adhesion molecules connect pre- and postsynaptic membranes and organize developing synapses. The regulation of these trans-synaptic interactions is an important neurobiological question. We have previously shown that the synaptic cell adhesion molecules (SynCAMs) 1 and 2 engage in homo- and heterophilic interactions and bridge the synaptic cleft to induce presynaptic terminals. Here, we demonstrate that site-specific N-glycosylation impacts the structure and function of adhesive SynCAM interactions. Through crystallographic analysis of SynCAM 2, we identified within the adhesive interface of its Ig1 domain an N-glycan on residue Asn(60). Structural modeling of the corresponding SynCAM 1 Ig1 domain indicates that its glycosylation sites Asn(70)/Asn(104) flank the binding interface of this domain. Mass spectrometric and mutational studies confirm and characterize the modification of these three sites. These site-specific N-glycans affect SynCAM adhesion yet act in a differential manner. Although glycosylation of SynCAM 2 at Asn(60) reduces adhesion, N-glycans at Asn(70)/Asn(104) of SynCAM 1 increase its interactions. The modification of SynCAM 1 with sialic acids contributes to the glycan-dependent strengthening of its binding. Functionally, N-glycosylation promotes the trans-synaptic interactions of SynCAM 1 and is required for synapse induction. These results demonstrate that N-glycosylation of SynCAM proteins differentially affects their binding interface and implicate post-translational modification as a mechanism to regulate trans-synaptic adhesion.

PubMed: 20739279
DOI: 10.1074/jbc.M110.120865

Experimental method

X-RAY DIFFRACTION (2.21 Å)