|Recommended name:||Transient receptor potential cation channel subfamily V member 1|
|Sequence length:||839 AA.|
|Enzyme regulation:||Channel activity is activated via the interaction with PIRT and phosphatidylinositol 4,5-bisphosphate (PIP2). Both PIRT and PIP2 are required to activate channel activity|
The transient receptor potential cation channel subfamily V member 1 (TRPV1) is a channel protein, which is activated by heat, protons and vanilloids. Expressed in neurons of the central and peripheral nervous system, it is involved in the detection and forwarding of painful physical and chemical stimuli.
If activated, the channel is permeable for cations as sodium, potassium and calcium ions which leads to the depolarisation of the sensory neuron. Usually, TRPV1 opens, if the temperature exceeds 42° Celsius, the pH value drops below 6 or if an agonistic ligand binds to a critical site.
The tachyphylaxis of the receptor can be modulated by multiple ligands as e.g. adenosine triphosphate (ATP) and calmodulin, which bind to a N-terminal ankyrin repeat domain. Topologically, the channel is a homo-tetramer that contains intracellular N- and C-terminal regions. Each monomer has six transmembrane helices that shape the central pore of the channel.
The binding site for vanilloids is believed to be located between the transmembrane segments S2 and S4. The temperature sensor is near the C-terminus of the protein and the voltage sensor is represented of a single arginin residue in S4.
Homology modeling was carried out after the description by Fernández-Ballester and Ferrer-Montiel (Molecular Models of TRPV1, 2008).
Due to reasons of complexity and reliability, we limited ourselves to modeling of the transmembrane domains of the channel.
First the transmembrane domains of both the template and target were identified using the TMHMM server. The template is a hetero-tetramer and its chain B was used for the alignment. Since the template shows very little identity with the target sequence (9.5%), the alignment had to be refined manually.
Here the SWISS-MODEL server in alignment mode was used to build the monomer. The assembly of the resulting monomer into a tetramer was performed using PyMOL.
After a loop of each monomer, which had been clashing with its neighbouring helices, was manually refined using Accelrys Discovery Studio, the energy minimization was calculated using GROMOS96 in the Swiss PDB Viewer environment.
The resulting homology model is displayed in an interactive view with JSmol in the following: