Sandbox Reserved 1093: Difference between revisions
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[[Image:LRRTM2 details.png|900px|left]] | [[Image:LRRTM2 details.png|900px|left]] | ||
'''<scene name='82/829346/Lrrtm2/5'>N-term fixation domain</scene>''' | |||
The N-terminal signal peptide is long of 33 amino. The extracellular domain contains 399 amino acids organized in 2 cysteine-rich domains (<scene name='82/829346/Lrrnt/1'>LRRNT</scene> and <scene name='82/829346/Lrrct/1'>LRRCT</scene>) and <scene name='82/829346/Lrr/2'>10 leucine rich domains</scene> (LRR). Each LRR domain is composed of 21 amino acids containing the conserved 11-aa sequence, LxxLxLxxN/ CxL, where x is any amino acid, and <scene name='82/829346/Leucine/1'>leucine</scene> and asparagine can be replaced with other hydrophobic residues. The leucine rich repeat domain forms a convex structure stabilized by a <scene name='82/829346/Phe/1'>Phe</scene> spine. The concave surface is composed of a continuous <scene name='82/829346/Beta_sheets/1'>β-sheet</scene>, which provides an effective ligand-binding site, whereas the convex surface consists of <scene name='82/829346/Alpha_helix/1'>α-helices</scene>, which affect the curvature of the LRR domain. | The N-terminal signal peptide is long of 33 amino. The extracellular domain contains 399 amino acids organized in 2 cysteine-rich domains (<scene name='82/829346/Lrrnt/1'>LRRNT</scene> and <scene name='82/829346/Lrrct/1'>LRRCT</scene>) and <scene name='82/829346/Lrr/2'>10 leucine rich domains</scene> (LRR). Each LRR domain is composed of 21 amino acids containing the conserved 11-aa sequence, LxxLxLxxN/ CxL, where x is any amino acid, and <scene name='82/829346/Leucine/1'>leucine</scene> and asparagine can be replaced with other hydrophobic residues. The leucine rich repeat domain forms a convex structure stabilized by a <scene name='82/829346/Phe/1'>Phe</scene> spine. The concave surface is composed of a continuous <scene name='82/829346/Beta_sheets/1'>β-sheet</scene>, which provides an effective ligand-binding site, whereas the convex surface consists of <scene name='82/829346/Alpha_helix/1'>α-helices</scene>, which affect the curvature of the LRR domain. | ||
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The fixation of Nrxns doesn’t change the conformation of the protein aside from Glu348 flipping toward the calcium ions. | The fixation of Nrxns doesn’t change the conformation of the protein aside from Glu348 flipping toward the calcium ions. | ||
'''Trans Membrane domain''' | |||
The transmembrane domain is a 21 amino acid long helical domain. | The transmembrane domain is a 21 amino acid long helical domain. | ||
'''C-term fixation domain''' | |||
The cytoplasmic domain contains 73 amino acids. It has been shown that the deletion of 55 residues from the C-terminal domain leads to abnormal intracellular trafficking pathway. This results in LRRTM2 being present everywhere in the cell. This domain also contains a PSD consensus cytoplasmic binding domain (ECEV) which binds PSD-95 [http://proteopedia.org/wiki/index.php/1tq3] (postsynaptic scaffolding protein) | The cytoplasmic domain contains 73 amino acids. It has been shown that the deletion of 55 residues from the C-terminal domain leads to abnormal intracellular trafficking pathway. This results in LRRTM2 being present everywhere in the cell. This domain also contains a PSD consensus cytoplasmic binding domain (ECEV) which binds PSD-95 [http://proteopedia.org/wiki/index.php/1tq3] (postsynaptic scaffolding protein) | ||
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LRRTM2 protein play a key role in the regulation of the synaptic fonctions and development by interracting with various proteins both inside and outside the neuron cell. | LRRTM2 protein play a key role in the regulation of the synaptic fonctions and development by interracting with various proteins both inside and outside the neuron cell. | ||
'''Interaction with extracellular proteins''' | |||
On the N-term fixation site, LRRTM2 binds specifically to Neurexin1 <scene name='82/829346/Neurexin_1_alpha/1'>α</scene> and <scene name='82/829346/Beta-neurexin_1/2'>β</scene> [http://proteopedia.org/wiki/index.php/Neurexin]. The affinity of the binding depends on the splicing of the insert SS4 of both neurexins. This binding plays a critical role in the formation of excitatory synapses as it briges the synaptic cleft. Without Neurexin1, LRRTM2 can't act on presynaptic differentiation leading to a reduction in the amount of excitatory synapses. In addition, the presynaptic receptors Neurexin 1 α and β are known to be receptors for <scene name='82/829346/Neurologin-neurexin/1'>Neurologin 1</scene> [http://proteopedia.org/wiki/index.php/3vkf], a protein similar to LRRTM2. Neurologin 1 also regulates the formation of excitatory synapses. | |||
'''Interaction with intracellular proteins''' | '''Interaction with intracellular proteins''' | ||
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It has also been noted that the repression of LRRTM2 induced a decrease in the density of PSD-95. Thus, LRRTM2 recruits PSD-95 at postsynaptic density and then binds to PSD-95 via the ECFV cytoplasmic motif. The interaction of PSD-95 with glutamate receptors, located at the postsynaptic membrane, as well as with other synaptic synaptic proteins. | It has also been noted that the repression of LRRTM2 induced a decrease in the density of PSD-95. Thus, LRRTM2 recruits PSD-95 at postsynaptic density and then binds to PSD-95 via the ECFV cytoplasmic motif. The interaction of PSD-95 with glutamate receptors, located at the postsynaptic membrane, as well as with other synaptic synaptic proteins. | ||
By the interaction with important postsynaptic components, LRRTM2 turns out to be crucial in the regulation of the postsynaptic fonctions and plasticity. | By the interaction with important postsynaptic components, LRRTM2 turns out to be crucial in the regulation of the postsynaptic fonctions and plasticity. | ||
[[Image:LRRTM2functions.png|1100px|left]] | [[Image:LRRTM2functions.png|1100px|left]] | ||