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	Mechanistic determinants and dynamics of cA6 synthesis in type III CRISPR-Cas effector complexes.
ジャーナル・号・ページ	Nucleic Acids Res, Vol. 53, Issue 2, Year 2025
掲載日	2025年1月11日
著者	Kenny Jungfer / Štefan Moravčík / Carmela Garcia-Doval / Anna Knörlein / Jonathan Hall / Martin Jinek /
PubMed 要旨	Type III clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems (type III CRISPR-Cas systems) use guide RNAs to recognize RNA transcripts of foreign ...Type III clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems (type III CRISPR-Cas systems) use guide RNAs to recognize RNA transcripts of foreign genetic elements, which triggers the generation of cyclic oligoadenylate (cOA) second messengers by the Cas10 subunit of the type III effector complex. In turn, cOAs bind and activate ancillary effector proteins to reinforce the host immune response. Type III systems utilize distinct cOAs, including cyclic tri- (cA3), tetra- (cA4) and hexa-adenylates (cA6). However, the molecular mechanisms dictating cOA product identity are poorly understood. Here we used cryoelectron microscopy to visualize the mechanism of cA6 biosynthesis by the Csm effector complex from Enterococcus italicus (EiCsm). We show that EiCsm synthesizes oligoadenylate nucleotides in 3'-5' direction using a set of conserved binding sites in the Cas10 Palm domains to determine the size of the nascent oligoadenylate chain. Our data also reveal that conformational dynamics induced by target RNA binding results in allosteric activation of Cas10 to trigger oligoadenylate synthesis. Mutations of a key structural element in Cas10 perturb cOA synthesis to favor cA3 and cA4 formation. Together, these results provide comprehensive insights into the dynamics of cOA synthesis in type III CRISPR-Cas systems and reveal key determinants of second messenger product selectivity, thereby illuminating potential avenues for their engineering.
リンク	Nucleic Acids Res / PubMed:39817514 / PubMed Central
手法	EM (単粒子)
解像度	2.72 - 3.38 Å
構造データ	51145 9g9a EMDB-51145, PDB-9g9a: CryoEM structure of Enterococcus italicus Csm-crRNA (3.2 complex) 手法: EM (単粒子) / 解像度: 2.83 Å 51146 9g9b EMDB-51146, PDB-9g9b: CryoEM structure of Enterococcus italicus Csm-crRNA (4.3) complex 手法: EM (単粒子) / 解像度: 3.07 Å 51147 9g9c EMDB-51147, PDB-9g9c: CryoEM structure of Enterococcus italicus Csm-crRNA-CTR (3.2) complex 手法: EM (単粒子) / 解像度: 2.72 Å 51148 9g9d EMDB-51148, PDB-9g9d: CryoEM structure of Enterococcus italicus Csm-crRNA-CTR (4.3) complex 手法: EM (単粒子) / 解像度: 2.9 Å 51149 9g9e EMDB-51149, PDB-9g9e: CryoEM structure of Enterococcus italicus Csm-crRNA complex bound to AMPNPP 手法: EM (単粒子) / 解像度: 2.87 Å 51150 9g9f EMDB-51150, PDB-9g9f: CryoEM structure of Enterococcus italicus Csm-crRNA-CTR complex bound to AMPNPP 手法: EM (単粒子) / 解像度: 2.93 Å 51151 9g9g EMDB-51151, PDB-9g9g: CryoEM structure of Enterococcus italicus Csm-crRNA-CTR1 complex (4.3) bound to AMPNPP 手法: EM (単粒子) / 解像度: 3.38 Å 51152 9g9h EMDB-51152, PDB-9g9h: CryoEM structure of Enterococcus italicus Csm-crRNA-CTR1 complex bound to pNppA3 and AMPNPP 手法: EM (単粒子) / 解像度: 2.99 Å 51153 9g9i EMDB-51153, PDB-9g9i: CryoEM structure of Enterococcus italicus Csm-crRNA-CTR2 complex bound to pNppA3 and AMPNPP 手法: EM (単粒子) / 解像度: 3.31 Å 51154 9g9j EMDB-51154, PDB-9g9j: CryoEM structure of Enterococcus italicus Csm-crRNA complex bound to pNppA3 and AMPNPP 手法: EM (単粒子) / 解像度: 3.05 Å 51155 9g9k EMDB-51155, PDB-9g9k: CryoEM structure of Enterococcus italicus Csm-crRNA-CTR2 complex (4.3) bound to AMPNPP 手法: EM (単粒子) / 解像度: 3.34 Å
化合物	ChemComp-ZAN: 5'-O-[(S)-hydroxy{[(S)-hydroxy(phosphonooxy)phosphoryl]amino}phosphoryl]adenosine / アデノシン5′-[α,β-イミド]三りん酸 ChemComp-MG: Unknown entry / マグネシウムジカチオン PDB-1ii9: CRYSTAL STRUCTURE OF THE ESCHERICHIA COLI ARSENITE-TRANSLOCATING ATPASE IN COMPLEX WITH AMP-PNP ChemComp-ANP: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP / AMP-PNP, エネルギー貯蔵分子類似体YM ChemComp-MN*: Unknown entry
由来	enterococcus italicus dsm 15952 (バクテリア) severe acute respiratory syndrome coronavirus 2 (ウイルス)
キーワード	RNA BINDING PROTEIN / Type III-A CRISPR-Cas RNA-guided nuclease Endoribonuclease cyclic oligoadenylate synthetase HD nuclease