6D7X
Crystal Structure of Rat TRPV6*-Y466A- in complex with brominated 2-Aminoethoxydiphenyl borate (2-APB-Br)
Summary for 6D7X
| Entry DOI | 10.2210/pdb6d7x/pdb |
| Descriptor | Transient receptor potential cation channel subfamily V member 6, CALCIUM ION, 2-aminoethyl (4-bromophenyl)phenylborinate, ... (4 entities in total) |
| Functional Keywords | ion channels, transporter, calcium channel, epithelial calcium channel, membrane protein, membrane protein-inhibitor complex, membrane protein/inhibitor |
| Biological source | Rattus norvegicus (Rat) |
| Total number of polymer chains | 1 |
| Total formula weight | 77639.81 |
| Authors | Singh, A.K.,Saotome, K.,McGoldrick, L.L.,Sobolevsky, A.I. (deposition date: 2018-04-25, release date: 2018-07-18, Last modification date: 2024-12-25) |
| Primary citation | Singh, A.K.,Saotome, K.,McGoldrick, L.L.,Sobolevsky, A.I. Structural bases of TRP channel TRPV6 allosteric modulation by 2-APB. Nat Commun, 9:2465-2465, 2018 Cited by PubMed Abstract: Transient receptor potential (TRP) channels are involved in various physiological processes, including sensory transduction. The TRP channel TRPV6 mediates calcium uptake in epithelia and its expression is dramatically increased in numerous types of cancer. TRPV6 inhibitors suppress tumor growth, but the molecular mechanism of inhibition remains unknown. Here, we present crystal and cryo-EM structures of human and rat TRPV6 bound to 2-aminoethoxydiphenyl borate (2-APB), a TRPV6 inhibitor and modulator of numerous TRP channels. 2-APB binds to TRPV6 in a pocket formed by the cytoplasmic half of the S1-S4 transmembrane helix bundle. Comparing human wild-type and high-affinity mutant Y467A structures, we show that 2-APB induces TRPV6 channel closure by modulating protein-lipid interactions. Mutagenesis and functional analyses suggest that the identified 2-APB binding site might be present in other members of vanilloid subfamily TRP channels. Our findings reveal a mechanism of ion channel allosteric modulation that can be exploited for therapeutic design. PubMed: 29941865DOI: 10.1038/s41467-018-04828-y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.6 Å) |
Structure validation
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