Crystal structure of Lon protease: molecular architecture of gated entry to a sequestered degradation chamber.
Lon proteases are distributed in all kingdoms of life and are required for survival of cells under stress. Lon is a tandem fusion of an AAA+ molecular chaperone and a protease with a serine-lysine catalytic dyad. We report the 2.0-Å resolution crystal structure of Thermococcus onnurineus NA1 Lon (TonLon). The structure is a three-tiered hexagonal cylinder with a large sequestered chamber accessible through an axial channel. Conserved loops extending from the AAA+ domain combine with an insertion domain containing the membrane anchor to form an apical domain that serves as a gate governing substrate access to an internal unfolding and degradation chamber. Alternating AAA+ domains are in tight- and weak-binding nucleotide states with different domain orientations and intersubunit contacts, reflecting intramolecular dynamics during ATP-driven protein unfolding and translocation. The bowl-shaped proteolytic chamber is contiguous with the chaperone chamber allowing internalized proteins direct access to the proteolytic sites without further gating restrictions.
Cha
Sun-Shin
SS
Marine Biotechnology Research Center, Korea Ocean Research and Development Institute, Ansan, Republic of Korea. chajung@kordi.re.kr
An
Young Jun
YJ
Lee
Chang Ro
CR
Lee
Hyun Sook
HS
Kim
Yeon-Gil
YG
Kim
Sang Jin
SJ
Kwon
Kae Kyoung
KK
De Donatis
Gian Marco
GM
Lee
Jung-Hyun
JH
Maurizi
Michael R
MR
Kang
Sung Gyun
SG
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D049070:Protease La / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D019712:Thermococcus / Q000201:enzymology
D001426:Bacterial Proteins; D049070:Protease La