Structure of Prokaryotic HslVU Protease-Chaperone Complex

Abstract

The HslVU is the prokaryotic, proteasome-related, ATP-dependent protein degrading machinery involved in the turnover of short-lived regulatory proteins. The HslVU is a two-component system in which the HslV protease that preferentially cleaves after Leu residues is activated by HslU, the ATPase and unfoldase. The subunits of HslU form a hexameric ring where as HslV subunits form a dodecamer of two-stacked hexameric rings. The quaternary structures of HslV and HslU constitute the HslVU complex in which HslV dodecamer forms a central barrel flanked at both ends by HslU hexamers. The HslU and HslV central pores are aligned in the complex and the proteolytic sites are sequestered in an internal chamber of HslV dodecamer. Several different crystal structures of the complex between HslV and HslU show alternative quaternary interfaces for the two components. During an ATP-dependent process, the HslU hexamer binds, unfolds and translocates the substrate proteins into the proteolytic chamber of HslV. The proteolytic (HslV) and regulatory (HslU) ‘compartments’ of HslVU system occur separately, however, HslU mediates the assembly of the functional complex after it recognizes a structured protein substrate.