Crystal structure of the N-terminal ankyrin repeat domain of TRPV3 reveals unique conformation of finger 3 loop critical for channel function
Protein & Cell
;
(12): 942-950, 2013.
Artigo
em Inglês
| WPRIM
| ID: wpr-757542
ABSTRACT
In all six members of TRPV channel subfamily, there is an ankyrin repeat domain (ARD) in their intracellular N-termini. Ankyrin (ANK) repeat, a common motif with typically 33 residues in each repeat, is primarily involved in protein-protein interactions. Despite the sequence similarity among the ARDs of TRPV channels, the structure of TRPV3-ARD, however, remains unknown. Here, we report the crystal structure of TRPV3-ARD solved at 1.95 Å resolution, which reveals six-ankyrin repeats. While overall structure of TRPV3-ARD is similar to ARDs from other members of TRPV subfamily; it, however, features a noticeable finger 3 loop that bends over and is stabilized by a network of hydrogen bonds and hydrophobic packing, instead of being flexible as seen in known TRPV-ARD structures. Electrophysiological recordings demonstrated that mutating key residues R225, R226, Q255, and F249 of finger 3 loop altered the channel activities and pharmacology. Taken all together, our findings show that TRPV3-ARD with characteristic finger 3 loop likely plays an important role in channel function and pharmacology.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fisiologia
/
Ligação Proteica
/
Conformação Proteica
/
Dados de Sequência Molecular
/
Modelos Moleculares
/
Química
/
Sequência de Aminoácidos
/
Homologia de Sequência de Aminoácidos
/
Estrutura Terciária de Proteína
/
Repetição de Anquirina
Tipo de estudo:
Estudo prognóstico
Limite:
Humanos
Idioma:
Inglês
Revista:
Protein & Cell
Ano de publicação:
2013
Tipo de documento:
Artigo
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