title: Interactions of PAN's C-termini with archaeal 20S proteasome and implications for the eukaryotic proteasome-ATPase interactions.
abstract: Protein degradation in the 20S proteasome is regulated in eukaryotes by the 19S ATPase complex and in archaea by the homologous PAN ATPase ring complex. Subunits of these hexameric ATPases contain on their C-termini a conserved hydrophobic-tyrosine-X (HbYX) motif that docks into pockets in the 20S to stimulate the opening of a gated substrate entry channel. Here, we report the crystal structure of the archaeal 20S proteasome in complex with the C-terminus of the archaeal proteasome regulatory ATPase, PAN. This structure defines the detailed interactions between the critical C-terminal HbYX motif and the 20S alpha-subunits and indicates that the intersubunit pocket in the 20S undergoes an induced-fit conformational change on binding of the HbYX motif. This structure together with related mutagenesis data suggest how in eukaryotes certain proteasomal ATPases bind to specific pockets in an asymmetrical manner to regulate gate opening.
authors.affiliation: The W.M. Keck Advanced Microscopy Laboratory, Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94132, USA.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Yu
authors.forename: David M
authors.initials: DM
authors.lastname: Smith
authors.forename: Ho Min
authors.initials: HM
authors.lastname: Kim
authors.forename: Victor
authors.initials: V
authors.lastname: Rodriguez
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Goldberg
authors.forename: Yifan
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs / Q000502:physiology; D001105:Archaea / Q000201:enzymology / Q000378:metabolism*; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D005057:Eukaryotic Cells / Q000201:enzymology / Q000378:metabolism*; D008958:Models, Molecular; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D020836:Protein Structure, Quaternary; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C402204:PA26 protein, Trypanosoma brucei; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C420334:PAN enzyme