Controlled destruction: AAA+ ATPases in protein degradation from bacteria to eukaryotes.
Energy-dependent protein degradation is carried out by bipartite assemblies of conserved architecture. A chaperone ring comprising ATPase domains of the AAA+ -type caps both ends of a hollow protease cylinder, thereby controlling access to the active sites. Hydrolysis of ATP is translated into a force that unfolds substrates and translocates them into the protease. Several recent advances reveal how the modular composition and cellular localization of these complexes contribute to their fine-tuned regulation. Crystal structures of the ubiquitin receptor Rpn13 as well as ClpS, the bacterial determinant of N-end rule degradation, in complex with their respective substrates demonstrate principles of substrate recognition by chaperone-proteases. Mechanistic studies show that polyubiquitin tags can act in trans to target nonubiquitinated substrates for degradation.
ETH Zürich, Institute of Molecular Biology & Biophysics, Zurich, Switzerland.
Frank
F
Striebel
Wolfgang
W
Kress
Eilika
E
Weber-Ban
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D025821:Polyubiquitin / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding
D019843:Archaeal Proteins; D001426:Bacterial Proteins; D046912:Multiprotein Complexes; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases