Structural highlights
Publication Abstract from PubMed
Synaptic adhesion molecules are key components in development of the brain, and in 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 sulphate proteoglycans, including glypican. We report here the crystal structure of a thermostabilized mouse LRRTM2, with a Tm 30 degrees C higher than the wild type protein. We localized the neurexin binding site to the concave surface based on protein engineering, sequence conservation and prior information on the ligand interaction 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 the wild type LRRTM1 and LRRTM2 for neurexin-beta1 with and without Ca2+. Cell culture studies and binding experiments show that the engineered protein is functional and capable of forming synapse-like contacts. The structural and functional data presented here provides the first structure of an LRRTM protein, and allows us to propose a model for molecular mechanism of LRRTM function in the synaptic adhesion.
Crystal structure of engineered LRRTM2 synaptic adhesion molecule and a model for neurexin binding.,Paatero A, Rosti K, Shkumatov AV, Sele C, Brunello C, Kysenius K, Singha P, Jokinen V, Huttunen H, Kajander T Biochemistry. 2016 Jan 19. PMID:26785044[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Paatero A, Rosti K, Shkumatov AV, Sele C, Brunello C, Kysenius K, Singha P, Jokinen V, Huttunen H, Kajander T. Crystal structure of engineered LRRTM2 synaptic adhesion molecule and a model for neurexin binding. Biochemistry. 2016 Jan 19. PMID:26785044 doi:https://dx.doi.org/10.1021/acs.biochem.5b00971
