Crystal Structures of β-Neurexin 1 and β-Neurexin 2 Ectodomains and Dynamics of Splice Insertion Sequence 4
Copyright policy )Crystal Structures of β-Neurexin 1 and β-Neurexin 2 Ectodomains and Dynamics of Splice Insertion Sequence 4
Presynaptic neurexins (NRXs) bind to postsynaptic neuroligins (NLs) to form Ca(2+)-dependent complexes that bridge neural synapses. beta-NRXs bind NLs through their LNS domains, which contain a single site of alternative splicing (splice site 4) giving rise to two isoforms: +4 and Delta. We present crystal structures of the Delta isoforms of the LNS domains from beta-NRX1 and beta-NRX2, crystallized in the presence of Ca(2+) ions. The Ca(2+)-binding site is disordered in the beta-NRX2 structure, but the 1.7 A beta-NRX1 structure reveals a single Ca(2+) ion, approximately 12 A from the splice insertion site, with one coordinating ligand donated by a glutamic acid from an adjacent beta-NRX1 molecule. NMR studies of beta-NRX1+4 show that the insertion sequence is unstructured, and remains at least partially disordered in complex with NL. These results raise the possibility that beta-NRX insertion sequence 4 may function in roles independent of neuroligin binding.
- Howard Hughes Medical Institute United States
- King’s University United States
- Columbia University United States
Models, Molecular, Sequence Homology, Amino Acid, PROTEINS, Cell Adhesion Molecules, Neuronal, Molecular Sequence Data, Membrane Proteins, Nerve Tissue Proteins, Crystallography, X-Ray, Models, Biological, Recombinant Proteins, Protein Structure, Tertiary, Rats, SIGNALING, Structural Biology, Animals, Protein Isoforms, Calcium, Amino Acid Sequence, RNA Splice Sites, Molecular Biology, Protein Binding
Models, Molecular, Sequence Homology, Amino Acid, PROTEINS, Cell Adhesion Molecules, Neuronal, Molecular Sequence Data, Membrane Proteins, Nerve Tissue Proteins, Crystallography, X-Ray, Models, Biological, Recombinant Proteins, Protein Structure, Tertiary, Rats, SIGNALING, Structural Biology, Animals, Protein Isoforms, Calcium, Amino Acid Sequence, RNA Splice Sites, Molecular Biology, Protein Binding
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