Structure of a Proteasome Pba1-Pba2 Complex

Stadtmueller, Beth M.; Kish-Trier, Erik; Ferrell, Katherine; Petersen, Charisse; Robinson, Howard; Myszka, David G.; Eckert, Debra M.; Formosa, Tim; Hill, Christopher P.

doi:10.1074/jbc.m112.367003

Cited by 57 publications

(47 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Structures of three specific yeast CP assembly intermediates bearing Pba1–Pba2 have been characterized: the “15S intermediate” (Ump1, Pba1–Pba2, all α and all β subunits except β7), the “preholoproteasome” (immature full CP plus Ump1 and Pba1–Pba2)[38], and a reconstituted Pba1–Pba2-CP complex[39] (Figure 3b). The first two structures were derived from negative-stain EM while the third was determined by X-ray crystallography.…”

Section: The 20s Core Particle (Cp)mentioning

confidence: 99%

“…It represents a snapshot of the interaction between Pba1–Pba2 and mature CP, presumably when Pba1–Pba2 is poised for release. Pba1–Pba2 has been shown to dissociate easily from mature CP at physiological salt concentrations[39]. Both Pba1 and Pba2 have a C-terminal HbYX (hydrophobic-tyrosine-any amino acid) motif[25], which is found in several proteasome activators and is required for the activators to interact with the α pocket formed by two adjacent α subunits.…”

Section: The 20s Core Particle (Cp)mentioning

confidence: 99%

See 1 more Smart Citation

Proteasome Structure and Assembly

Budenholzer

Cheng

et al. 2017

Journal of Molecular Biology

315

280

View full text Add to dashboard Cite

The eukaryotic 26S proteasome is a large multi-subunit complex that degrades the majority of proteins in the cell under normal conditions. The 26S proteasome can be divided into two subcomplexes: the 19S regulatory particle (RP) and the 20S core particle (CP). Most substrates are first covalently modified by ubiquitin, which then directs them to the proteasome. The function of the RP is to recognize, unfold, deubiquitylate and translocate substrates into the CP, which contains the proteolytic sites of the proteasome. Given the abundance and subunit complexity of the proteasome, the assembly of this ~2.5 MDa complex must be carefully orchestrated to ensure its correct formation. In recent years, significant advances have been made in the understanding of proteasome assembly, structure and function. Technical advances in cryo-electron microscopy have resulted in a series of atomic cryo-EM structures of both human and yeast 26S proteasomes. These structures have illuminated new intricacies and dynamics of the proteasome. In this review, we focus on the mechanisms of proteasome assembly, particularly in light of recent structural information.

show abstract

Section: The 20s Core Particle (Cp)mentioning

confidence: 99%

Section: The 20s Core Particle (Cp)mentioning

confidence: 99%

Proteasome Structure and Assembly

Budenholzer

Cheng

et al. 2017

Journal of Molecular Biology

315

280

View full text Add to dashboard Cite

show abstract

“…3A and C) (PDB accession number 3VR0). Another PAC2 family protein, the yeast proteasome assembly chaperone Pba1 (27), is 10% identical with Rv2125 at the amino acid sequence level. They are structurally similar, with an RMSD of 3.8 Å over 200 C␣ atoms (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The HbYX motif is conserved in archaeal and eukaryotic proteasome activators, whether they are ATP dependent (such as PAN and Rpt1 to Rpt6) or ATP independent (such as PA26 and PA28) (13). Both yeast Pba1 and Pba2 have the HbYX motif, and they form a heterodimer that binds mature 20S CP with those motifs (24,27). Known M. tuberculosis proteasome activators, such as the ATP-dependent Mpa and the ATPindependent PafE, have a C-terminal GQYL motif that is functionally equivalent to the archaeal and eukaryotic HbYX motif (14,31).…”

Section: Resultsmentioning

confidence: 99%

“…Considering that the M. tuberculosis proteasome system has several parallels to the eukaryotic system, we considered whether Rv2125 and Rv2715 function as bacterial proteasome assembly chaperones. We conducted biochemical and structural studies of Rv2125 and found that it has an overall fold similar to that of members of the PAC2 family, including the archaeal proteasome activator PbaB and the yeast proteasome assembly chaperone Pba1 (25,27). However, we found that neither Rv2125 nor Rv2714 (whose crystal structure was determined previously) (28) interacted with proteasome core particles.…”

mentioning

confidence: 89%

See 1 more Smart Citation

Structural Analysis of Mycobacterium tuberculosis Homologues of the Eukaryotic Proteasome Assembly Chaperone 2 (PAC2)

et al. 2017

View full text Add to dashboard Cite

A previous bioinformatics analysis identified the Mycobacterium tuberculosis proteins Rv2125 and Rv2714 as orthologs of the eukaryotic proteasome assembly chaperone 2 (PAC2). We set out to investigate whether Rv2125 or Rv2714 can function in proteasome assembly. We solved the crystal structure of Rv2125 at a resolution of 3.0 Å, which showed an overall fold similar to that of the PAC2 family proteins that include the archaeal PbaB and the yeast Pba1. However, Rv2125 and Rv2714 formed trimers, whereas PbaB forms tetramers and Pba1 dimerizes with Pba2. We also found that purified Rv2125 and Rv2714 could not bind to M. tuberculosis 20S core particles. Finally, proteomic analysis showed that the levels of known proteasome components and substrate proteins were not affected by disruption of Rv2125 in M. tuberculosis. Our work suggests that Rv2125 does not participate in bacterial proteasome assembly or function.IMPORTANCE Although many bacteria do not encode proteasomes, M. tuberculosis not only uses proteasomes but also has evolved a posttranslational modification system called pupylation to deliver proteins to the proteasome. Proteasomes are essential for M. tuberculosis to cause lethal infections in animals; thus, determining how proteasomes are assembled may help identify new ways to combat tuberculosis. We solved the structure of a predicted proteasome assembly factor, Rv2125, and isolated a genetic Rv2125 mutant of M. tuberculosis. Our structural, biochemical, and genetic studies indicate that Rv2125 and Rv2714 do not function as proteasome assembly chaperones and are unlikely to have roles in proteasome biology in mycobacteria.

show abstract

The Biogenesis of the Eukaryotic Proteasome

Kusmierczyk

2014

The Molecular Chaperones Interaction Networks in Protein Folding and Degradation

View full text Add to dashboard Cite

Structure of a Proteasome Pba1-Pba2 Complex

Cited by 57 publications

References 40 publications

Proteasome Structure and Assembly

Proteasome Structure and Assembly

Structural Analysis of Mycobacterium tuberculosis Homologues of the Eukaryotic Proteasome Assembly Chaperone 2 (PAC2)

The Biogenesis of the Eukaryotic Proteasome

Contact Info

Product

Resources

About