Structural Elements Regulating AAA+ Protein Quality Control Machines

Frontiers in Molecular Biosciences
Chiung-Wen ChangFrancis T F Tsai

Abstract

Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins. In this mini-review, we will discuss structural elements present in AAA+ proteins involved in protein quality control, drawing similarities to their known role in substrate interaction by AAA+ proteins involved in DNA translocation. Elements to be discussed include the pore loop-1, the Inter-Subunit Signaling (ISS) motif, and the Pre-Sensor I insert (PS-I) motif. Lastly, we will summarize our current understanding on the inter-relationship of those structural elements and propose a model how ATP binding and hydrolysis might be coupled to polypeptide translocation in protein quality control machines.

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Citations

Oct 11, 2019·Protein Science : a Publication of the Protein Society·Stephanie N Gates, Andreas Martin
Dec 19, 2019·Proceedings of the National Academy of Sciences of the United States of America·Yi-Chin Candace TsaiOliver Mueller-Cajar
Aug 5, 2019·Mitochondrion·Tyler E Steele, Steven E Glynn
Oct 12, 2021·Critical Reviews in Biochemistry and Molecular Biology·Yousuf A KhanAxel T Brunger

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Datasets Mentioned

BETA
GM111084

Methods Mentioned

BETA
ISS

Software Mentioned

PROMALS3D

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