TRPV1 (transient receptor potential cation channel, subfamily V, member 1)

The canonical form comprises 839 aa (MW~96 kDa) and is composed of six transmembrane spanning domains and a pore forming region between transmembrane domains 5 and 6. The N-terminal and C-terminal tails are in cytoplasmatic side. Three N terminal ankyrin (ANK) repeats are present in N-terminal tail. The variant form TRPV1b is identical to TRPV1 except for the partial deletion of the third ankyrin repeat domain and adjoining polypeptide sequence. Aminoacid modifications has been found (according to Swiss-Prot) in different residues (Table 1). The N-terminal intracellular domain appears to play a pivotal role in intracellular activation of TRPV1, in fact, by mutagenesis analysis a loss of sensitivity to capsaicin has been found related to residue Tyr-511 (Gavva et al., 2004). Modification of a single N-terminal cysteine altered activation of TRPV1 by pungent compounds ranging from onions to garlic (Salazar et al., 2008). The N-terminal intracellular domain also interacts with adjacent modulatory proteins and with the C-terminal intracellular domain. In the closed state, the N-terminal domain is likely exposed to the binding of ATP and a C-terminal region residues interact with PIP-2, facilitating channel activation. In contrast, a desensitized state may be promoted through the interaction of the N- and C-terminal domains through modulatory action involving calcium-calmodulin interacting regions. Moreover, the ankyrin repeat domains residing within the N-terminal intracellular domain forming a region of three repeats spanning amino acids participating in protein-protein (subunit) interactions (Bork, 1993). The presence of concave binding surfaces for ATP within the ANK regions suggest a role of ANKs in modulating channel activation and function (Lishko et al., 2007).