title: Slicing a protease: structural features of the ATP-dependent Lon proteases gleaned from investigations of isolated domains.
abstract: ATP-dependent Lon proteases are multi-domain enzymes found in all living organisms. All Lon proteases contain an ATPase domain belonging to the AAA(+) superfamily of molecular machines and a proteolytic domain with a serine-lysine catalytic dyad. Lon proteases can be divided into two subfamilies, LonA and LonB, exemplified by the Escherichia coli and Archaeoglobus fulgidus paralogs, respectively. The LonA subfamily is defined by the presence of a large N-terminal domain, whereas the LonB subfamily has no such domain, but has a membrane-spanning domain that anchors the protein to the cytoplasmic side of the membrane. The two subfamilies also differ in their consensus sequences. Recent crystal structures for several individual domains and sub-fragments of Lon proteases have begun to illuminate similarities and differences in structure-function relationships between the two subfamilies. Differences in orientation of the active site residues in several isolated Lon protease domains point to possible roles for the AAA(+) domains and/or substrates in positioning the catalytic residues within the active site. Structures of the proteolytic domains have also indicated a possible hexameric arrangement of subunits in the native state of bacterial Lon proteases. The structure of a large segment of the N-terminal domain has revealed a folding motif present in other protein families of unknown function and should lead to new insights regarding ways in which Lon interacts with substrates or other cellular factors. These first glimpses of the structure of Lon are heralding an exciting new era of research on this ancient family of proteases.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow.
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Rotanova
authors.forename: Istvan
authors.initials: I
authors.lastname: Botos
authors.forename: Edward E
authors.initials: EE
authors.lastname: Melnikov
authors.forename: Fatima
authors.initials: F
authors.lastname: Rasulova
authors.forename: Alla
authors.initials: A
authors.lastname: Gustchina
authors.forename: Michael R
authors.initials: MR
authors.lastname: Maurizi
authors.forename: Alexander
authors.initials: A
authors.lastname: Wlodawer
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D019611:Archaeoglobus fulgidus / Q000201:enzymology; D001665:Binding Sites / Q000235:genetics; D016384:Consensus Sequence / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry; D008958:Models, Molecular; D049070:Protease La / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: D029968:Escherichia coli Proteins; D000255:Adenosine Triphosphate; C483567:Lon protein, E coli; D049070:Protease La