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-Structure paper
タイトル | Two-Step Activation Mechanism of the ClpB Disaggregase for Sequential Substrate Threading by the Main ATPase Motor. |
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ジャーナル・号・ページ | Cell Rep, Vol. 27, Issue 12, Page 3433-33446.e4, Year 2019 |
掲載日 | 2019年6月18日 |
著者 | Célia Deville / Kamila Franke / Axel Mogk / Bernd Bukau / Helen R Saibil / |
PubMed 要旨 | AAA+ proteins form asymmetric hexameric rings that hydrolyze ATP and thread substrate proteins through a central channel via mobile substrate-binding pore loops. Understanding how ATPase and ...AAA+ proteins form asymmetric hexameric rings that hydrolyze ATP and thread substrate proteins through a central channel via mobile substrate-binding pore loops. Understanding how ATPase and threading activities are regulated and intertwined is key to understanding the AAA+ protein mechanism. We studied the disaggregase ClpB, which contains tandem ATPase domains (AAA1, AAA2) and shifts between low and high ATPase and threading activities. Coiled-coil M-domains repress ClpB activity by encircling the AAA1 ring. Here, we determine the mechanism of ClpB activation by comparing ATPase mechanisms and cryo-EM structures of ClpB wild-type and a constitutively active ClpB M-domain mutant. We show that ClpB activation reduces ATPase cooperativity and induces a sequential mode of ATP hydrolysis in the AAA2 ring, the main ATPase motor. AAA1 and AAA2 rings do not work synchronously but in alternating cycles. This ensures high grip, enabling substrate threading via a processive, rope-climbing mechanism. |
リンク | Cell Rep / PubMed:31216466 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.4 - 6.2 Å |
構造データ | EMDB-4621: ClpB (DWB and K476C mutant) bound to casein in presence of ATPgammaS - state KC-3 EMDB-4622: EMDB-4623: EMDB-4624, PDB-6qs6: EMDB-4625: EMDB-4626, PDB-6qs7: EMDB-4627, PDB-6qs8: EMDB-4940, PDB-6rn2: |
化合物 | ChemComp-AGS: ChemComp-ADP: ChemComp-MG: |
由来 |
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キーワード | CHAPERONE / disaggregase / proteostasis / AAA |