Structural Insights into the Allosteric Operation of the Lon AAA+ Protease.
Structure
; 24(5): 667-675, 2016 05 03.
Article
em En
| MEDLINE
| ID: mdl-27041592
ABSTRACT
The Lon AAA+ protease (LonA) is an evolutionarily conserved protease that couples the ATPase cycle into motion to drive substrate translocation and degradation. A hallmark feature shared by AAA+ proteases is the stimulation of ATPase activity by substrates. Here we report the structure of LonA bound to three ADPs, revealing the first AAA+ protease assembly where the six protomers are arranged alternately in nucleotide-free and bound states. Nucleotide binding induces large coordinated movements of conserved pore loops from two pairs of three non-adjacent protomers and shuttling of the proteolytic groove between the ATPase site and a previously unknown Arg paddle. Structural and biochemical evidence supports the roles of the substrate-bound proteolytic groove in allosteric stimulation of ATPase activity and the conserved Arg paddle in driving substrate degradation. Altogether, this work provides a molecular framework for understanding how ATP-dependent chemomechanical movements drive allosteric processes for substrate degradation in a major protein-destruction machine.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Mitocondriais
/
Proteases Dependentes de ATP
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Sítio Alostérico
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article