Structural understanding of the transmembrane domains of inositol triphosphate receptors and ryanodine receptors towards calcium channeling.
Inositol 1,4,5-triphosphate receptors (Insp(3)Rs) and ryanodine receptors (ryRs) act as cationic channels transporting calcium ions from the endoplasmic reticulum to cytosol by forming tetramers and are proteins localized to the endoplasmic reticulum (ER). Despite the absence of classical calcium-binding motifs, calcium channeling occurs at the transmembrane domain. We have investigated putative calcium binding motifs in these sequences. Prediction methods indicate the presence of six transmembrane helices in the C-terminal domain, one of the three domains conserved between Insp(3)R and ryR receptors. The recently identified crystal structure of the K(+) channel, which also forms tetramers, revealed that two transmembrane helices, an additional pore helix and a selectivity filter are responsible for selective K(+) ion channeling. The last three TM helices of Insp(3)R and ryR are particularly well conserved and we found analogous pore helix and selectivity filter motif in these sequences. We obtained a three-dimensional structural model for the transmembrane tetramer by extrapolating the distant structural similarity to the K(+) channels.
Shah
P K
PK
National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bangalore 560 065, India.
Sowdhamini
R
R
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011188:Potassium / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry*; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D011188:Potassium; D002118:Calcium