EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural mechanisms of TRPM7 activation and inhibition.
ジャーナル・号・ページ	Nat Commun, Vol. 14, Issue 1, Page 2639, Year 2023
掲載日	2023年5月8日
著者	Kirill D Nadezhdin / Leonor Correia / Chamali Narangoda / Dhilon S Patel / Arthur Neuberger / Thomas Gudermann / Maria G Kurnikova / Vladimir Chubanov / Alexander I Sobolevsky /
PubMed 要旨	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.
リンク	Nat Commun / PubMed:37156763 / PubMed Central
手法	EM (単粒子)
解像度	2.17 - 2.99 Å
構造データ	40496 8si2 EMDB-40496, PDB-8si2: Cryo-EM structure of TRPM7 in MSP2N2 nanodisc in apo state 手法: EM (単粒子) / 解像度: 2.19 Å 40497 8si3 EMDB-40497, PDB-8si3: Cryo-EM structure of TRPM7 in GDN detergent in apo state 手法: EM (単粒子) / 解像度: 2.61 Å 40498 8si4 EMDB-40498, PDB-8si4: Cryo-EM structure of TRPM7 N1098Q mutant in GDN detergent in open state 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 2.91 Å 40505 8sib EMDB-40505, PDB-8sib: Cryo-EM structure of TRPM7 MHR1-3 domain 手法: EM (単粒子) / 解像度: 2.62 Å
化合物	ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / リン脂質YM ChemComp-CLR: CHOLESTEROL / コレステロ-ル 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 / ナトリウムカチオン ChemComp-HOH: WATER ChemComp-CA: Unknown entry / カルシウムジカチオン 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 / ナルトリベン 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 / VER-155008 ChemComp-6RA*: N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-1H-benzimidazol-2-amine / NS-8593
由来	mus musculus (ハツカネズミ)
キーワード	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