Structural Insights into the Allosteric Operation of the Lon AAA+ Protease
Journal
Structure (London, England : 1993)
Journal Volume
24
Journal Issue
5
Pages
667
Date Issued
2016-05-03
Author(s)
Lin, Chien-Chu
Su, Shih-Chieh
Su, Ming-Yuan
Feng, Chia-Cheng
Wu, Shih-Hsiung
Chang, Chung-I
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.
Subjects
AAA+ protease; ATPase cycle; LonA; allosteric regulation; crystal structure; pore loops; protein degradation; translocation
SDGs
Type
journal article