Structural Elements Regulating AAA+ Protein Quality Control Machines

• Main Authors: Chiung-Wen Chang, Sukyeong Lee, Francis T. F. Tsai
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2017-05-01
• Series: Frontiers in Molecular Biosciences
• Subjects: AAA+ proteins; protein quality control; Pre-Sensor I insert; inter-subunit signaling motif; pore loop
• Online Access: http://journal.frontiersin.org/article/10.3389/fmolb.2017.00027/full

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.