title: The crystal structure of apo-FtsH reveals domain movements necessary for substrate unfolding and translocation.
abstract: The hexameric membrane-spanning ATP-dependent metalloprotease FtsH is universally conserved in eubacteria, mitochondria, and chloroplasts, where it fulfills key functions in quality control and signaling. As a member of the self-compartmentalizing ATPases associated with various cellular activities (AAA+ proteases), FtsH converts the chemical energy stored in ATP via conformational rearrangements into a mechanical force that is used for substrate unfolding and translocation into the proteolytic chamber. The crystal structure of the ADP state of Thermotoga maritima FtsH showed a hexameric assembly consisting of a 6-fold symmetric protease disk and a 2-fold symmetric AAA ring. The 2.6 A resolution structure of the cytosolic region of apo-FtsH presented here reveals a new arrangement where the ATPase ring shows perfect 6-fold symmetry with the crucial pore residues lining an open circular entrance. Triggered by this conformational change, a substrate-binding edge beta strand appears within the proteolytic domain. Comparison of the apo- and ADP-bound structure visualizes an inward movement of the aromatic pore residues and generates a model of substrate translocation by AAA+ proteases. Furthermore, we demonstrate that mutation of a conserved glycine in the linker region inactivates FtsH.
authors: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.
authors: Christoph
authors: C
authors: Bieniossek
authors: Barbara
authors: B
authors: Niederhauser
authors: Ulrich M
authors: UM
authors: Baumann
mesh_terms: D049069:ATP-Dependent Proteases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D020134:Catalytic Domain; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D017931:DNA Primers; D008958:Models, Molecular; D011487:Protein Conformation; D011489:Protein Denaturation; D021381:Protein Transport; D013379:Substrate Specificity; D020124:Thermotoga maritima / Q000201:enzymology*
chemical_list: D017931:DNA Primers; D049069:ATP-Dependent Proteases