6DMW

Calmodulin-bound full-length rbTRPV5

6DMW の概要

• エントリーDOI: 10.2210/pdb6dmw/pdb
• EMDBエントリー: 7967
• 分子名称: Transient receptor potential cation channel subfamily V member 5, Calmodulin-1, CALCIUM ION (3 entities in total)
• 機能のキーワード: calmodulin, trpv5, full-length, calcium channel, transport protein
• 由来する生物種: Oryctolagus cuniculus (Rabbit); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 348571.40

構造登録者

Hughes, T.E.T.,Pumroy, R.A.,Moiseenkova-Bell, V.Y. (登録日: 2018-06-05, 公開日: 2018-10-24, 最終更新日: 2024-03-13)

主引用文献

Hughes, T.E.T.,Pumroy, R.A.,Yazici, A.T.,Kasimova, M.A.,Fluck, E.C.,Huynh, K.W.,Samanta, A.,Molugu, S.K.,Zhou, Z.H.,Carnevale, V.,Rohacs, T.,Moiseenkova-Bell, V.Y.
Structural insights on TRPV5 gating by endogenous modulators.
Nat Commun, 9:4198-4198, 2018

PubMed Abstract: TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P and CaM. The PI(4,5)P structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-π interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery.

PubMed: 30305626
DOI: 10.1038/s41467-018-06753-6

実験手法

ELECTRON MICROSCOPY (4.4 Å)