Substrate-translocating loops regulate mechanochemical coupling and power production in AAA+ protease ClpXP
| Autor: | Piere Rodriguez-Aliaga, Luis Ramirez, Frank Kim, Andreas Martin, Carlos Bustamante |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Proteases Protein Conformation medicine.medical_treatment ATPase Biophysics Medical and Health Sciences Article Substrate Specificity 03 medical and health sciences Adenosine Triphosphate Models Structural Biology ATP hydrolysis Escherichia coli medicine Molecular Biology Protein Unfolding Adenosine Triphosphatases Protease biology Chemistry Escherichia coli Proteins Hydrolysis Burst phase Molecular Substrate (chemistry) Endopeptidase Clp Biological Sciences Cell biology Adenosine Diphosphate Kinetics 030104 developmental biology Proteostasis Proteasome Chemical Sciences biology.protein ATPases Associated with Diverse Cellular Activities Molecular Chaperones Protein Binding Developmental Biology |
| Zdroj: | Nature structural & molecular biology, vol 23, iss 11 |
| ISSN: | 1545-9985 1545-9993 |
| DOI: | 10.1038/nsmb.3298 |
| Popis: | Single-molecule spectroscopy reveals the complete mechanochemical cycle of the AAA+ protease ClpXP: ADP release and ATP binding occur during the dwell phase, whereas ATP hydrolysis and Pi release occur during the burst phase. ATP-dependent proteases of the AAA+ family, including Escherichia coli ClpXP and the eukaryotic proteasome, contribute to maintenance of cellular proteostasis. ClpXP unfolds and translocates substrates into an internal degradation chamber, using cycles of alternating dwell and burst phases. The ClpX motor performs chemical transformations during the dwell and translocates the substrate in increments of 1–4 nm during the burst, but the processes occurring during these phases remain unknown. Here we characterized the complete mechanochemical cycle of ClpXP, showing that ADP release and ATP binding occur nonsequentially during the dwell, whereas ATP hydrolysis and phosphate release occur during the burst. The highly conserved translocating loops within the ClpX pore are optimized to maximize motor power generation, the coupling between chemical and mechanical tasks, and the efficiency of protein processing. Conformational resetting of these loops between consecutive bursts appears to determine ADP release from individual ATPase subunits and the overall duration of the motor's cycle. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink