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A conserved strategy for structure change and energy transduction in Hsp104 and other AAA+ protein motors.

ABSTRACT: The vast superfamily of massively large AAA+ protein molecular machines functions to convert the chemical energy of cytosolic ATP into physico-mechanical form and use it to perform an extraordinary number of physical operations on proteins, nucleic acids, and membrane systems. Cryo-EM studies now reveal some aspects of substrate handling at high resolution, but the broader interpretation of AAA+ functional properties is still opaque. This paper integrates recent hydrogen exchange results for the typical AAA+ protein Hsp104 with prior information on several near and distantly related others. The analysis points to a widely conserved functional strategy. Hsp104 cycles through a long-lived loosely-structured energy-input "open" state that releases spent ADP and rebinds cytosolic ATP. ATP binding energy is transduced by allosteric structure change to poise the protein at a high energy level in a more tightly structured "closed" state. The briefly occupied energy-output closed state binds substrate strongly and is catalytically-active. ATP hydrolysis permits energetically downhill structural relaxation which is coupled to drive the energy-requiring substrate processing process. Other AAA+ proteins appear to cycle through states that are analogous functionally if not in structural detail. These results revise the current model for AAA+ function, explain the structural basis of single molecule optical tweezer kinetic phases, identify the separate energetic roles of ATP binding and hydrolysis, and specify a sequence of structural and energetic events that carry AAA+ proteins unidirectionally around a functional cycle to propel their diverse physical tasks.

SUBMITTER: Ye X

PROVIDER: S-EPMC8449053 | biostudies-literature |

REPOSITORIES: biostudies-literature

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