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Neurotrophins & NTs Receptors. Loredana Lombardi Ariadna Laguna. Molecular Mechanisms of Development (EMBO), Barcelona 2006. Neurotrophins : Ligands, Receptors and their pleiotropic role in Development. Cell Death. Cell Survival, Growth and Differentiation. Aim.
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Neurotrophins & NTs Receptors Loredana Lombardi Ariadna Laguna Molecular Mechanisms of Development (EMBO), Barcelona 2006
Neurotrophins: Ligands, Receptors and their pleiotropic role in Development Cell Death Cell Survival, Growth and Differentiation
Aim Analyse the sequences of neurotrophins and their receptors using bioinformatic tools to better understand their biological properties. Procedure • Retrieve protein sequences from databases (mouse) • Align protein sequences • Search for known protein domains • Search for post-translational modifications in NTs • Search for phosphorylation sites and possible binding partners in Trks
2-3) Align protein sequences and search for known protein domains Prosite, Pfam, Motifscan,SMART Clustalw, Multialign, Boxshade Signal Peptide Glycosilation (Asparagine) Propeptide NGF domain Disulfid Bonds
2-3) Analyse p75 protein sequence and search for known protein domains Prosite, Pfam, Motifscan,SMART Signal Peptide Trans Membrane Domain TMPRED PSIPRED DEATH Domain 4 TNFR Domains
2-3) Align protein sequences and search for known protein domains Prosite, Pfam, Motifscan,SMART Clustalw, Multialign, Boxshade Signal Peptide Leucine Rich IgG like domain
2-3) Align protein sequences and search for known protein domains Prosite, Pfam, Motifscan,SMART Clustalw, Multialign, Boxshade TransMembrane Domain TMPRED PSIPRED ATP binding site Tyrosine Kinase Domain Activation Loop Predicted P-Tyr NetPhos 2.0 Server
5) Search for phosphorylation sites and possible binding partners in Trks SCANSITE TrkA
Conclusions We found some discrepancies between different servers in the predicted protein domains essential to compare different predictions !!! We found a good correspondance between different servers in the most conserved domains NGF domain in NT and PTyrK domain in Trks It is useful to predict post-translational modifications and phosphorylation sites with bioinformatic tools to later manipulate the protein in the lab.