PMID- 20543817
OWN - NLM
STAT- MEDLINE
DCOM- 20100820
LR  - 20211020
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 29
IP  - 14
DP  - 2010 Jul 21
TI  - Structural insights into the exquisite selectivity of neurexin/neuroligin 
      synaptic interactions.
PG  - 2461-71
LID - 10.1038/emboj.2010.123 [doi]
AB  - The extracellular domains of neuroligins and neurexins interact through Ca(2+) to 
      form flexible trans-synaptic associations characterized by selectivity for 
      neuroligin or neurexin subtypes. This heterophilic interaction, essential for 
      synaptic maturation and differentiation, is regulated by gene selection, 
      alternative mRNA splicing and post-translational modifications. A new, 2.6 
      A-resolution crystal structure of a soluble neurexin-1beta-neuroligin-4 
      (Nrx1beta-NL4) complex permits a detailed description of the Ca(2+)-coordinated 
      interface and unveils concerted positional rearrangements of several residues of 
      NL4, not observed in neuroligin-1, associated with Nrx1beta binding. Surface 
      plasmon resonance analysis of the binding of structure-guided Nrx1beta mutants 
      towards NL4 and neuroligin-1 shows that flexibility of the Nrx1beta-binding site 
      in NL4 is reflected in a greater dissociation constant of the complex and higher 
      sensitivity to ionic strength and pH variations. Analysis of neuroligin mutants 
      points to critical functions for two respective residues in neuroligin-1 and 
      neuroligin-2 in governing the affinity of the complexes. Although neuroligin-1 
      and neuroligin-2 have pre-determined conformations that respectively promote and 
      prevent Nrx1beta association, unique conformational reshaping of the NL4 surface 
      is required to permit Nrx1beta association.
FAU - Leone, Philippe
AU  - Leone P
AD  - Architecture et Fonction des Macromolecules Biologiques, CNRS/Universite 
      d'Aix-Marseille, Campus Luminy, Marseille, France.
FAU - Comoletti, Davide
AU  - Comoletti D
FAU - Ferracci, Geraldine
AU  - Ferracci G
FAU - Conrod, Sandrine
AU  - Conrod S
FAU - Garcia, Simon U
AU  - Garcia SU
FAU - Taylor, Palmer
AU  - Taylor P
FAU - Bourne, Yves
AU  - Bourne Y
FAU - Marchot, Pascale
AU  - Marchot P
LA  - eng
GR  - P0-1 ES 10337/ES/NIEHS NIH HHS/United States
GR  - P42 ES010337/ES/NIEHS NIH HHS/United States
GR  - R37-GM 18360/GM/NIGMS NIH HHS/United States
GR  - AS2617/AS/Autism Speaks/United States
GR  - R37 GM018360/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100611
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Adhesion Molecules, Neuronal)
RN  - 0 (Membrane Proteins)
RN  - 0 (NLGN4X protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 156532-80-8 (neurexin Ibeta)
SB  - IM
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Carrier Proteins/*chemistry/genetics/metabolism
MH  - Cell Adhesion Molecules, Neuronal
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Membrane Proteins/*chemistry/genetics/metabolism
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/*chemistry/genetics/metabolism
MH  - Protein Binding
MH  - Protein Processing, Post-Translational
MH  - *Protein Structure, Tertiary
MH  - Sequence Alignment
MH  - Surface Plasmon Resonance
MH  - Synapses/*metabolism/ultrastructure
PMC - PMC2910273
COIS- The authors declare that they have no conflict of interest.
EDAT- 2010/06/15 06:00
MHDA- 2010/08/21 06:00
PMCR- 2011/07/21
CRDT- 2010/06/15 06:00
PHST- 2010/02/02 00:00 [received]
PHST- 2010/05/17 00:00 [accepted]
PHST- 2010/06/15 06:00 [entrez]
PHST- 2010/06/15 06:00 [pubmed]
PHST- 2010/08/21 06:00 [medline]
PHST- 2011/07/21 00:00 [pmc-release]
AID - emboj2010123 [pii]
AID - 10.1038/emboj.2010.123 [doi]
PST - ppublish
SO  - EMBO J. 2010 Jul 21;29(14):2461-71. doi: 10.1038/emboj.2010.123. Epub 2010 Jun 
      11.