14. Neuropilin 2 is a transmembrane receptor protein shown in the following figu

Question

14. Neuropilin 2 is a transmembrane receptor protein shown in the following figure. Based on what you know about amino acid side chains, describe which groups of amino acids you expect to find in the following regions: A. SEMA binding domain VEGF binding domain Transmembrane domain Cytoplasmic domain Explain if a mutation causing a change from N> R in the cytoplasmic domain would be detrimental to the protein structure a. b. c. d. e. SEMA binding subdomains b1 VEGF binding subdomains b2 Transmembrane domain Cytoplasmic domain PDZ

Explanation / Answer

Neuropilin 2 is a single-pass transmembrane protein encoded by the gene nrp2 gene. This protein plays an important role in cardiovascular development, axon guidance and tumorigenesis. Many isoforms are also present for nrp gene. Structurally, its acts as a transmembrane protein for two ligand types, the semaphorin (SEMA) family of axon guidance mediators and Vascular endothelial growth factor (VEGF) family of stimulators for angiogenesis. There are varying groups of amino acids present in the different structural regions of neuropilin 2 protein.

a) SEMA binding domain : Semaphorin proteins are unique in having a 'sema domain' in their N-terminal end, characterized by approximately 500 amino acids with 14-16 conserved cysteines.

b) VEGF binding domain: VEGF is a part of PDGF (Platelet Derived Growth Factor) family of proteins. VEGF is found as a dimeric glycoprotein with monomers conserved with 8 residues of Cysteine. These cysteine residues for essential intramolecular and intermolecular disulfide bonding form a folded loop-like structure, essential for interacting with tyrosine kinases. This interaction is important for angiogenesis by VEGF. Other conserved amino acid domains are Arginine-82, Lysine-84 and Histidine-86.

c) Transmembrane domain: The transmembrane domain is rich in aromatic amino acids like Phenylalanine and Tryrosine. It is also rich in hydrophobic amino acids like Cysteine, because the hydrophobic side chains readily pass through the plasma membrane, which is hydrophobic in nature.

d) Cytoplasmic domain: The cytoplasmic domain is rich in hydrophobic amino acids like Cysteine. It is essential for the endocytosis of transmembrane protein and also for signal transduction.

d) Any mutation in the regions of the Cytoplasmic domain would result in variation in the amino acid content. This adversely affects the functioning of the neuropilin. The Ca2+ binding sites become non-functional resulting in blocking of signal transduction. It also results in blocking the activity of tyrosine kinase receptors as their determinant sites get altered.

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