SASDBH3: Leucine-rich repeat transmembrane neuronal protein 2, LRRTM2 (fra...

Basic information

• Entry: Database: SASBDB / ID: SASDBH3

Sample

Leucine-rich repeat transmembrane neuronal protein 2, LRRTM2 (fragment 30-380)

• Mouse Leucine-rich repeat transmembrane neuronal protein 2, LRRTM2 (protein), LRRTM2 30-380, Mus musculus

Function / homology

Function:

: / Neurexins and neuroligins / : / regulation of postsynaptic density assembly / neurexin family protein binding / negative regulation of receptor internalization / anchoring junction / positive regulation of synapse assembly / excitatory synapse / GABA-ergic synapse / hippocampal mossy fiber to CA3 synapse / long-term synaptic potentiation / synapse organization / Schaffer collateral - CA1 synapse / membrane => GO:0016020 / glutamatergic synapse / extracellular space

Domain/homology:

Leucine rich repeat / Leucine-rich repeat, typical subtype / Leucine-rich repeats, typical (most populated) subfamily / Leucine-rich repeat profile. / Leucine-rich repeat / Leucine-rich repeat domain superfamily

Component:

Leucine-rich repeat transmembrane neuronal protein 2

• Biological species: Mus musculus (house mouse)
• Citation: Journal: Biochemistry / Year: 2016; Title: Crystal Structure of an Engineered LRRTM2 Synaptic Adhesion Molecule and a Model for Neurexin Binding.; Authors: Anja Paatero / Katja Rosti / Alexander V Shkumatov / Celeste Sele / Cecilia Brunello / Kai Kysenius / Prosanta Singha / Ville Jokinen / Henri Huttunen / Tommi Kajander / ; Abstract: 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.

Contact author

• Alexander Shkumatov (VUB, Vrije Universiteit Brussel, Pleinlaan 2 1050 Brussel)

Models

• Model #446: ; Type: dummy / Radius of dummy atoms: 4.75 A / Chi-square value: 1.387 / P-value: 0.099700; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Leucine-rich repeat transmembrane neuronal protein 2, LRRTM2 (fragment 30-380); Specimen concentration: 1.30-3.40
• Buffer: Name: 20 mM Tris 150 mM NaCl 3% glycerol / Concentration: 20.00 mM / pH: 7.4 / Composition: 150 mM NaCl, 3% glycerol

Entity #297

Name: LRRTM2 30-380 / Type: protein
Description: Mouse Leucine-rich repeat transmembrane neuronal protein 2, LRRTM2
Formula weight: 40.122 / Num. of mol.: 2 / Source: Mus musculus / References: UniProt: Q8BGA3
Sequence:

LGMACPPKCR CEKLLFYCDS QGFHSVPNAT DKGSLGLSLR HNHITALERD QFASFSQLTW LHLDHNQIST VKEDAFQGLY KLKELILSSN KIFYLPNTTF TQLINLQNLD LSFNQLSSLH PELFYGLRKL QTLHLRSNSL RTIPVRLFWD CRSLEFLDLS TNRLRSLARN GFAGLIKLRE LHLEHNQLTK INFAHFLRLS SLHTLFLQWN KISNLTCGMD WTWSTLEKLD LTGNEIKAID LTVFETMPNL KILLMDNNKL NSLDSKILNS LKSLTTVGLS GNLWECSPRV CALASWLGSF QGRWEHSILC HSPDHTQGED ILDAVHGFQL CWNLSTTVTA MATTYRDPTT E

Experimental information

• Beam: Instrument name: ESRF ID14-3 / City: Grenoble / 国: France / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.09 Å / Dist. spec. to detc.: 2.87 mm
• Detector: Name: Pilatus 1M

Scan

Title: Mouse Leucine-rich TM protein LRRTM2 / Measurement date: Jun 28, 2015 / Storage temperature: 10 °C / Exposure time: 1 sec. / Number of frames: 10 / Unit: 1/nm /

	Min	Max
Q	0.1032	4.5009

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 924 /

	Min	Max
Q	0.159677	4.50089
P(R) point	1	924
R	0	21.6

Result

D max: 21.6 / Type of curve: single_conc /

	Experimental	Porod
MW	88.2 kDa	74.2 kDa

	P(R)	Guinier
Forward scattering, I0	69.5	67.4
Radius of gyration, Rg	4.54 nm	4.15 nm