4G4S

Structure of Proteasome-Pba1-Pba2 Complex

Summary for 4G4S

• Entry DOI: 10.2210/pdb4g4s/pdb
• Related PRD ID: PRD_000907
• Descriptor: Proteasome component C7-alpha, Proteasome component PUP3, Proteasome component C11, ... (19 entities in total)
• Functional Keywords: alpha beta, ntn-hydrolase, peptide binding, hydrolase-chaperone complex, hydrolase/chaperone
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Cellular location: Cytoplasm: P21243 P25451 P22141 P30656 P23724 P30657 Q05778 P36040 P23639 P23638 P40303 P32379 P40302 P21242 P38624 P25043
• Total number of polymer chains: 16
• Total formula weight: 426627.26

Authors

Kish-Trier, E.,Robinson, H.,Stadtmueller, B.M.,Hill, C.P. (deposition date: 2012-07-16, release date: 2012-09-05, Last modification date: 2024-10-09)

Primary citation

Stadtmueller, B.M.,Kish-Trier, E.,Ferrell, K.,Petersen, C.N.,Robinson, H.,Myszka, D.G.,Eckert, D.M.,Formosa, T.,Hill, C.P.
Structure of a Proteasome Pba1-Pba2 Complex: IMPLICATIONS FOR PROTEASOME ASSEMBLY, ACTIVATION, AND BIOLOGICAL FUNCTION.
J.Biol.Chem., 287:37371-37382, 2012

PubMed Abstract: The 20S proteasome is an essential, 28-subunit protease that sequesters proteolytic sites within a central chamber, thereby repressing substrate degradation until proteasome activators open the entrance/exit gate. Two established activators, Blm10 and PAN/19S, induce gate opening by binding to the pockets between proteasome α-subunits using C-terminal HbYX (hydrophobic-tyrosine-any residue) motifs. Equivalent HbYX motifs have been identified in Pba1 and Pba2, which function in proteasome assembly. Here, we demonstrate that Pba1-Pba2 proteins form a stable heterodimer that utilizes its HbYX motifs to bind mature 20S proteasomes in vitro and that the Pba1-Pba2 HbYX motifs are important for a physiological function of proteasomes, the maintenance of mitochondrial function. Other factors that contribute to proteasome assembly or function also act in the maintenance of mitochondrial function and display complex genetic interactions with one another, possibly revealing an unexpected pathway of mitochondrial regulation involving the Pba1-Pba2 proteasome interaction. Our determination of a proteasome Pba1-Pba2 crystal structure reveals a Pba1 HbYX interaction that is superimposable with those of known activators, a Pba2 HbYX interaction that is different from those reported previously, and a gate structure that is disrupted but not sufficiently open to allow entry of even small peptides. These findings extend understanding of proteasome interactions with HbYX motifs and suggest multiple roles for Pba1-Pba2 interactions throughout proteasome assembly and function.

PubMed: 22930756
DOI: 10.1074/jbc.M112.367003

Experimental method

X-RAY DIFFRACTION (2.49 Å)