Selective adaptor dependent protein degradation in bacteria

Abstract

Energy dependent proteolysis is essential for all life, but uncontrolled degradation leads to devastating consequences. In bacteria, oligomeric AAA+ proteases are responsible for controlling protein destruction and are regulated in part by adaptor proteins. Adaptors are regulatory factors that shape protease substrate choice by either restricting or enhancing substrate recognition in several ways. In some cases, protease activity or assembly itself requires adaptor binding. Adaptors can also alter specificity by acting as scaffolds to tether particular substrates to already active proteases. Finally, hierarchical assembly of adaptors can use combinations of several activities to enhance the protease’s selectivity. Because the lifetime of the constituent proteins directly affects the duration of a particular signaling pathway, regulated proteolysis impacts almost all cellular responses. In this review, we describe recent progress in regulated protein degradation, focusing on fundamental principles of adaptors and how they perform critical biological functions, such as promoting cell cycle progression and quality control.

Consequences of the loss of catalytic triads in chloroplast CLPPR protease core complexes in vivo

“…ATP‐dependent Clp proteases are present in bacteria, as well as mitochondria and plastids (organelles of bacterial origin), where they regulate accumulation levels of a broad range of substrates (Alexopoulos, Guarne, & Ortega, ; Liu, Ologbenla, & Houry, ; Nishimura, Kato, & Sakamoto, ; Nishimura & van Wijk, ; Sauer & Baker, ). The first step in the CLP degradation process requires the recognition of substrates by the CLP AAA+ chaperones, possibly aided by specific adaptors (also named recognins) that recognize and deliver specific substrates (Kuhlmann & Chien, ; Mahmoud & Chien, ). The ATP‐dependent CLP chaperones then dock onto CLP protease core complexes consisting of two stacked heptameric rings, and unfold and direct substrates into the CLP protease complex (Olivares, Baker, & Sauer, ).…”

Reduction in adaptor amounts establishes degradation hierarchy among protease substrates

“…ATP-dependent proteases consist of two subunits or domains: one that uses the energy derived from ATP hydrolysis to unfold and shuttle substrates into the other subunit or domain where proteolysis actually takes place (1). Degradation of particular substrates of a given protease often requires adaptor proteins to recognize such substrates and deliver them to the unfoldase (2,3). We now report that enteric bacteria achieve differential degradation of substrates of the ATP-dependent protease ClpAP by altering the amounts of the adaptor protein ClpS under specific stress conditions.…”

On the Origins of Symmetry and Modularity in the Proteasome Family

“…Without a larger regulatory network, HslV coexists with a set of bacterial self‐compartmentalizing proteases, each with its own proteolytic scope. These proteases rely on specific substrate recognition modes of their associated AAA+ unfoldases, which typically recognize specific peptide sequences or receive substrates via specialized adaptor proteins . Hence, the change in symmetry not only broke with the established interactors but also allowed for the establishment of an independent regulatory layer accompanied by a shift in substrate recognition.…”

“…Apparently, also this transition led to a decrease in complexity, as BPH does not seem to utilize further regulatory layers that would restrict access to the proteolytic compartment. Consequently, BPH is expected to select target proteins via intrinsic specificity or through adaptor proteins and may have a more specialized substrate spectrum—as for Anbu, the other potentially ungated member of the family. These contemplations point to the necessity to reinvent substrate recognition at each evolutionary branch point.…”

“…The composition of the cellular proteome is tightly regulated through timely protein synthesis and degradation. In this framework, targeted protein degradation is primarily carried out by the heterologous group of self‐compartmentalizing proteases: large, symmetric barrel‐shaped assemblies that consist of several stacked multi‐subunit rings . While the number of rings, and thus the complexity of the system, differs between the various representatives, they all have a central double ring of proteolytic subunits, which confines the proteolytic activity in a central cavity that is shielded from the bulk solvent and only accessible through the narrow channels formed by the pores of the rings.…”