7èmes Journées Scientifiques de l’IFR Jean Roche en Biologie des Interactions Cellulaires,
Marseille, 21-23 Novembre 2007
Crystal structure of the post-synaptic cell adhesion protein, neuroligin.
Structure cristalline d’une neuroligine, protéine synaptique d’adhésion
cellulaire.
Igor Fabrichny 1,2, Davide Comoletti 3, Gerlind Sulzenbacher 2, Sandrine
Conrod 1, Palmer Taylor 3, Yves Bourne 2, & Pascale Marchot 1
1
Biochimie des Interactions Moléculaires et Cellulaires (BIMC), CNRS
FRE-2738, IFR Jean Roche, Université de la Méditerranée, Marseille.
2
Architecture et Fonction des Macromolécules Biologiques, CNRS UMR6098, Campus Luminy, Marseille.
3
Skaggs School of Pharmacy and Pharmaceutical Sciences, UCSD, La
Jolla, CA.
The neuroligins are postsynaptic cell adhesion proteins that associate with
their presynaptic partners, the beta-neurexins. Polymorphisms of the coding
regions of the neuroligin and neurexin genes (including point mutations,
truncations, and exon deletions) were recently found to be associated with
autism and mental retardation, indicating a strong genetic link to neurodevelopmental disorders. The limited affinity (high Kd value) recorded
between neuroligin and neurexin appears consistent with a labile complex
participating into plasticity events at the synapse.
From a recombinant, soluble form of the neuroligin extracellular domain
with simplified N- and O-glycosylation patterns and expressed in eukaryotic
cells, a 2.2 Å resolution crystal structure was obtained. This structure shows
the same dimeric assembly of subunits as found for the neuroligin cousin,
acetylcholinesterase; permits a detailed analysis of those structural features
that distinguish the neuroligins from the other members of the alpha/betahydrolase fold family of proteins (e.g., lipases and cholinesterases); and
highlights the position of surface determinants which other studies pointed
to be critical for neurexin interaction. This structure will be presented and
discussed in the view of a SAXS analysis of the overall shape and
dimensions of a neurexin-neuroligin complex [1].
[1] Comoletti D, Grishaev A, Whitten AE, Tsigelny I, Taylor P, &
Trewhella J (2007) Synaptic arrangement of the neuroligin/beta-neurexin
complex revealed by X-ray and neutron scattering. Structure 15, 693-705.
Supported by the SPINE2-Complexes Consortium to YB and PM, the CNRS
and FRM to IF and PM, the NAAR and CAN Pilot Research Award to DC,
and the USPHS and NIEHS to PT.