1. Structural insights into modulation and selectivity of transsynaptic neurexin–LRRTM interaction
- Author
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Shuya Fukai, Atsushi Yamagata, Takeshi Uemura, Katsumi Maenaka, Takashi Saitoh, Sakurako Goto-Ito, Asami Maeda, Masahiko Watanabe, Tomoko Shiroshima, Tomoyuki Yoshida, Tohru Terada, and Yusuke Sato
- Subjects
0301 basic medicine ,Cell Adhesion Molecules, Neuronal ,Science ,Neurexin ,General Physics and Astronomy ,Nerve Tissue Proteins ,LRRTM1 ,Plasma protein binding ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Postsynaptic potential ,Animals ,Humans ,Amino Acid Sequence ,lcsh:Science ,Neural Cell Adhesion Molecules ,Multidisciplinary ,Chemistry ,Calcium-Binding Proteins ,Alternative splicing ,HEK 293 cells ,Membrane Proteins ,General Chemistry ,Transmembrane protein ,Cell biology ,HEK293 Cells ,030104 developmental biology ,Synapses ,Excitatory postsynaptic potential ,Mutant Proteins ,lcsh:Q ,030217 neurology & neurosurgery ,Protein Binding - Abstract
Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) function as postsynaptic organizers that induce excitatory synapses. Neurexins (Nrxns) and heparan sulfate proteoglycans have been identified as presynaptic ligands for LRRTMs. Specifically, LRRTM1 and LRRTM2 bind to the Nrxn splice variant lacking an insert at the splice site 4 (S4). Here, we report the crystal structure of the Nrxn1β–LRRTM2 complex at 3.4 Å resolution. The Nrxn1β–LRRTM2 interface involves Ca2+-mediated interactions and overlaps with the Nrxn–neuroligin interface. Together with structure-based mutational analyses at the molecular and cellular levels, the present structural analysis unveils the mechanism of selective binding between Nrxn and LRRTM1/2 and its modulation by the S4 insertion of Nrxn., Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) function as postsynaptic organizers that induce excitatory synapses. Here authors solve the crystal structure of LRRTM2 in complex with its ligand Nrxn1β and shed light on how selective binding of ligands to LRRTM1/2 is achieved.
- Published
- 2018