8SIA
Cryo-EM structure of TRPM7 N1098Q mutant in GDN detergent in complex with inhibitor NS8593 in closed state
Summary for 8SIA
| Entry DOI | 10.2210/pdb8sia/pdb |
| Related | 8SI2 8SI3 8SI4 8SI5 8SI6 8SI7 8SI8 |
| EMDB information | 40496 40497 40498 40499 40500 40501 40502 40504 |
| Descriptor | Transient receptor potential cation channel subfamily M member 7, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, 2-[2-[(1~{S},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S})-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icos-18-ene-6,2'-oxane]-16-yl]oxyethyl]propane-1,3-diol, ... (6 entities in total) |
| Functional Keywords | transient receptor potential m family member 7, trp, channel, trpm7, trp channels, membrane protein, magnesium channel, inhibitor, ligand, ns8593 |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 4 |
| Total formula weight | 631842.57 |
| Authors | Nadezhdin, K.D.,Neuberger, A.,Sobolevsky, A.I. (deposition date: 2023-04-14, release date: 2023-05-17, Last modification date: 2024-10-16) |
| Primary citation | Nadezhdin, K.D.,Correia, L.,Narangoda, C.,Patel, D.S.,Neuberger, A.,Gudermann, T.,Kurnikova, M.G.,Chubanov, V.,Sobolevsky, A.I. Structural mechanisms of TRPM7 activation and inhibition. Nat Commun, 14:2639-2639, 2023 Cited by PubMed Abstract: The transient receptor potential channel TRPM7 is a master regulator of the organismal balance of divalent cations that plays an essential role in embryonic development, immune responses, cell mobility, proliferation, and differentiation. TRPM7 is implicated in neuronal and cardiovascular disorders, tumor progression and has emerged as a new drug target. Here we use cryo-EM, functional analysis, and molecular dynamics simulations to uncover two distinct structural mechanisms of TRPM7 activation by a gain-of-function mutation and by the agonist naltriben, which show different conformational dynamics and domain involvement. We identify a binding site for highly potent and selective inhibitors and show that they act by stabilizing the TRPM7 closed state. The discovered structural mechanisms provide foundations for understanding the molecular basis of TRPM7 channelopathies and drug development. PubMed: 37156763DOI: 10.1038/s41467-023-38362-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.91 Å) |
Structure validation
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