Crystal structure of the ATPase domain of the human AAA+ protein paraplegin/SPG7.
Paraplegin is an m-AAA protease of the mitochondrial inner membrane that is linked to hereditary spastic paraplegias. The gene encodes an FtsH-homology protease domain in tandem with an AAA+ homology ATPase domain. The protein is believed to form a hexamer that uses ATPase-driven conformational changes in its AAA-domain to deliver substrate peptides to its protease domain. We present the crystal structure of the AAA-domain of human paraplegin bound to ADP at 2.2 A. This enables assignment of the roles of specific side chains within the catalytic cycle, and provides the structural basis for understanding the mechanism of disease mutations.


BACKGROUND
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Structural Genomics Consortium, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Tobias
T
Karlberg
Susanne
S
van den Berg
Martin
M
Hammarström
Johanna
J
Sagemark
Ida
I
Johansson
Lovisa
L
Holmberg-Schiavone
Herwig
H
Schüler
D000074183:ATPases Associated with Diverse Cellular Activities; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray / Q000379:methods; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008666:Metalloendopeptidases / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D010455:Peptides; D008666:Metalloendopeptidases; C112889:SPG7 protein, human; C114583:m-AAA proteases; D000074183:ATPases Associated with Diverse Cellular Activities