Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural mechanisms of TRPM7 activation and inhibition.
Journal, issue, pages	Nat Commun, Vol. 14, Issue 1, Page 2639, Year 2023
Publish date	May 8, 2023
Authors	Kirill D Nadezhdin / Leonor Correia / Chamali Narangoda / Dhilon S Patel / Arthur Neuberger / Thomas Gudermann / Maria G Kurnikova / Vladimir Chubanov / Alexander I Sobolevsky /
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 ...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.
External links	Nat Commun / PubMed:37156763 / PubMed Central
Methods	EM (single particle)
Resolution	2.17 - 2.99 Å
Structure data	40496 8si2 EMDB-40496, PDB-8si2: Cryo-EM structure of TRPM7 in MSP2N2 nanodisc in apo state Method: EM (single particle) / Resolution: 2.19 Å 40497 8si3 EMDB-40497, PDB-8si3: Cryo-EM structure of TRPM7 in GDN detergent in apo state Method: EM (single particle) / Resolution: 2.61 Å 40498 8si4 EMDB-40498, PDB-8si4: Cryo-EM structure of TRPM7 N1098Q mutant in GDN detergent in open state Method: EM (single particle) / Resolution: 2.46 Å 40499 8si5 EMDB-40499, PDB-8si5: Cryo-EM structure of TRPM7 in MSP2N2 nanodisc in complex with agonist naltriben in open state Method: EM (single particle) / Resolution: 2.17 Å 40500 8si6 EMDB-40500, PDB-8si6: Cryo-EM structure of TRPM7 in MSP2N2 nanodisc in complex with agonist naltriben in closed state Method: EM (single particle) / Resolution: 2.44 Å 40501 8si7 EMDB-40501, PDB-8si7: Cryo-EM structure of TRPM7 in GDN detergent in complex with inhibitor VER155008 in closed state Method: EM (single particle) / Resolution: 2.59 Å 40502 8si8 EMDB-40502, PDB-8si8: Cryo-EM structure of TRPM7 N1098Q mutant in GDN detergent in complex with inhibitor VER155008 in closed state Method: EM (single particle) / Resolution: 2.99 Å 40504 8sia EMDB-40504, PDB-8sia: Cryo-EM structure of TRPM7 N1098Q mutant in GDN detergent in complex with inhibitor NS8593 in closed state Method: EM (single particle) / Resolution: 2.91 Å 40505 8sib EMDB-40505, PDB-8sib: Cryo-EM structure of TRPM7 MHR1-3 domain Method: EM (single particle) / Resolution: 2.62 Å
Chemicals	ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipidYM / POPC ChemComp-CLR: CHOLESTEROL / Cholesterol ChemComp-DU0: 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 ChemComp-NA: Unknown entry ChemComp-HOH: WATER / Water ChemComp-CA: Unknown entry ChemComp-ZY8: (4bS,8R,8aS,14bR)-7-(cyclopropylmethyl)-5,6,7,8,9,14b-hexahydro-8aH-4,8-methanobis[1]benzofuro[3,2-e:2',3'-g]isoquinoline-1,8a-diol ChemComp-3FD: 4-[[(2R,3S,4R,5R)-5-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-3,4-dihydroxy-oxolan-2-yl]methoxymethyl]benzonitrile ChemComp-6RA*: N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-1H-benzimidazol-2-amine
Source	mus musculus (house mouse)
Keywords	MEMBRANE PROTEIN / transient receptor potential M family member 7 / TRP / channel / TRPM7 / TRP channels / magnesium channel / N1098Q / open state / agonist / ligand / naltriben / inhibitor / VER155008 / NS8593