Structural models of α-neurexin. The diagram visualizes conformations
that the extracellular domain of α-neurexin can assume. In the U-form
(modeled from PDB ID: 3R05; left) only cerebellin (Cbln), neurexophilin (Nxph) and
dystroglycan (DAG) might bind to LNS6 and LNS2, respectively. After rotation of
about 180° in the αLNS5-αLNS6 hinge (modeled using PDB ID: 3ASI and
3R05; right), the core structure and αLNS6 become elongated and accessible to
additional ligands, including neuroligins (Nlgn) and leucine-rich repeat molecules
(LRRTM). The parentheses indicate the required presence (+) or absence (−)
of the splice inserts in αLNS6 (SS#4) or αLNS2 (SS#2). Coordinates for
αLNS1 have been modeled by sequence homology to other LNS domains because its
electron density map was not resolved in the crystal structure [60]. Intracellularly, cytosolic proteins such as synaptotagmin (Syt),
protein 4.1 from brain (4.1 m), CASK, Mint and Veli bind to the disordered
carboxy-terminal domain of neurexins. LNS domains, green (numbered 1 to 6);
EGF-like domains, yellow; splice inserts at splice sites #1 to #5, red. EGF,
epidermal growth factor-like; LNS, laminin-neurexin-sex hormone binding
globulin.