 |
PDBsum entry 3b3q
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cell adhesion
|
PDB id
|
|
|
|
3b3q
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural basis for synaptic adhesion mediated by neuroligin-Neurexin interactions.
|
|
|
Authors
|
|
X.Chen,
H.Liu,
A.H.Shim,
P.J.Focia,
X.He.
|
|
|
Ref.
|
|
Nat Struct Biol, 2008,
15,
50-56.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The heterophilic synaptic adhesion molecules neuroligins and neurexins are
essential for establishing and maintaining neuronal circuits by modulating the
formation and maturation of synapses. The neuroligin-neurexin adhesion is
Ca2+-dependent and regulated by alternative splicing. We report a structure of
the complex at a resolution of 2.4 A between the mouse neuroligin-1 (NL1)
cholinesterase-like domain and the mouse neurexin-1beta (NX1beta) LNS (laminin,
neurexin and sex hormone-binding globulin-like) domain. The structure revealed a
delicate neuroligin-neurexin assembly mediated by a hydrophilic, Ca2+-mediated
and solvent-supplemented interface, rendering it capable of being modulated by
alternative splicing and other regulatory factors. Thermodynamic data supported
a mechanism wherein splicing site B of NL1 acts by modulating a salt bridge at
the edge of the NL1-NX1beta interface. Mapping neuroligin mutations implicated
in autism indicated that most such mutations are structurally destabilizing,
supporting deficient neuroligin biosynthesis and processing as a common cause
for this brain disorder.
|
|
|
|
|
|
|
|
Figure 1.
(a) His-tag pull-down assay showing effects of mutagenesis of
NX1  surface
residues on NL1 binding.
|
|
Figure 5.
The mutated residues, NL1 Asp106 (corresponding to the NL4
G99S mutation), NL1 Lys414 (corresponding to the NL4 K378R
mutation), NL1 Arg473 (corresponding to the NL3 R451C mutation)
and NL1 Val439 (corresponding to the NL4 V403M mutation), are
colored green and shown in space-filling representation, and are
mapped on the NL1–NX1 complex
(ribbons). These residues are away from the binding and
dimerization interfaces, and are mostly buried.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2008,
15,
50-56)
copyright 2008.
|
|
|
|
|
|
|
