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PDBsum entry 5a5c
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Signaling protein
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PDB id
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5a5c
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References listed in PDB file
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Key reference
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Title
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Crystal structure of an engineered lrrtm2 synaptic adhesion molecule and a model for neurexin binding.
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Authors
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A.Paatero,
K.Rosti,
A.V.Shkumatov,
C.Sele,
C.Brunello,
K.Kysenius,
P.Singha,
V.Jokinen,
H.Huttunen,
T.Kajander.
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Ref.
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Biochemistry, 2016,
55,
914-926.
[DOI no: ]
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PubMed id
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Abstract
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Synaptic adhesion molecules are key components in development of the brain, and
in the formation of neuronal circuits, as they are central in the assembly and
maturation of chemical synapses. Several families of neuronal adhesion molecules
have been identified such as the neuronal cell adhesion molecules, neurexins and
neuroligins, and in particular recently several leucine-rich repeat proteins,
e.g., Netrin G-ligands, SLITRKs, and LRRTMs. The LRRTMs form a family of four
proteins. They have been implicated in excitatory glutamatergic synapse function
and were specifically characterized as ligands for neurexins in excitatory
synapse formation and maintenance. In addition, LRRTM3 and LRRTM4 have been
found to be ligands for heparan sulfate proteoglycans, including glypican. We
report here the crystal structure of a thermostabilized mouse LRRTM2, with a Tm
30 °C higher than that of the wild-type protein. We localized the neurexin
binding site to the concave surface based on protein engineering, sequence
conservation, and prior information about the interaction of the ligand with
neurexins, which allowed us to propose a tentative model for the LRRTM-neurexin
interaction complex. We also determined affinities of the thermostabilized
LRRTM2 and wild-type LRRTM1 and LRRTM2 for neurexin-β1 with and without Ca(2+).
Cell culture studies and binding experiments show that the engineered protein is
functional and capable of forming synapselike contacts. The structural and
functional data presented here provide the first structure of an LRRTM protein
and allow us to propose a model for the molecular mechanism of LRRTM function in
the synaptic adhesion.
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