Reading coordinates from the Protein Data Bank

Proteasome

An ATP-driven shredder that pulls tagged proteins apart

Summary

The proteasome destroys proteins that the cell marks with a ubiquitin chain. A ring of six AAA+ ATPases grips the marked protein, pulls it straight, and feeds it into a barrel. Three catalytic sites inside the barrel cut the chain into short peptides. A lid subunit strips the ubiquitin tag off in the same cycle.

Where: Cytosol and nucleus of all eukaryotes. Archaea and some bacteria have a simpler 20S core.
Power: ATP hydrolysis by six AAA+ subunits, in a set order around the ring

2.5 MDa

Mass of the holoenzyme10

Stated for the human 26S proteasome, not measured in this paper.

Core particle subunits1

Four rings of seven: (alpha1-7 beta1-7)2.

Catalytic sites per core1

Three per half barrel, on beta1, beta2 and beta5.

N-terminal threonine

Catalytic residue3

Deleting Thr1 or changing it to alanine stops the enzyme.

ATPase subunits9

Rpt1 to Rpt6 form the ring that grips and pulls the substrate.

3-22 residues

Peptide product length14

Product length follows a log-normal distribution.

~13 s

Time to degrade one tagged protein15

Measured for polyubiquitinated dihydrofolate reductase. A tighter fold takes about twice as long.

50-80 ATP

ATP cost per tagged protein15

Measured for Ub5-DHFR. Tighter folds cost more.

Resolved states of one working sample10

Seven conformations at 2.8-3.6 A, from ubiquitin recognition to translocation.

How it works

Big picture

Evidence

Sources

Other checked entries

1RYP
Yeast 20S core particle
The reference core particle. Two copies of each of the 14 subunits build the (alpha1-7 beta1-7)2 barrel.
1G0U
Yeast 20S, gated channel
The gated-channel structure. No subunit mutation is recorded, so it shows the gate of the wild-type core.
2F16
Yeast 20S with bortezomib
Shows which subunits the clinical drug blocks, and how a boronic acid binds the N-terminal threonine.
5LE5
Human 20S core particle
The human core at 1.8 A, for a species comparison with yeast.
5LF3
Human 20S with bortezomib
The drug bound to the human target. It anchors the subunit numbering used for human inhibitor design.
1PMA
Archaeal 20S proteasome
The simplest core particle: two subunit types, 14 copies each. It shows the ancestral state of the barrel.
6MSB
Human 26S proteasome, state EA1
One of seven states from a single substrate-engaged sample. State EA1 is a frame of the translocation cycle and shares chain names with the other six.
6MSD
Human 26S proteasome, state EA2
One of seven states from a single substrate-engaged sample. State EA2 is a frame of the translocation cycle and shares chain names with the other six.
6MSE
Human 26S proteasome, state EB
One of seven states from a single substrate-engaged sample. State EB is a frame of the translocation cycle and shares chain names with the other six.
6MSG
Human 26S proteasome, state EC1
One of seven states from a single substrate-engaged sample. State EC1 is a frame of the translocation cycle and shares chain names with the other six.
6MSH
Human 26S proteasome, state EC2
One of seven states from a single substrate-engaged sample. State EC2 is a frame of the translocation cycle and shares chain names with the other six.
6MSJ
Human 26S proteasome, state ED1
One of seven states from a single substrate-engaged sample. State ED1 is a frame of the translocation cycle and shares chain names with the other six.
6MSK
Human 26S proteasome, state ED2
One of seven states from a single substrate-engaged sample. State ED2 is a frame of the translocation cycle and shares chain names with the other six.
6EF3
Yeast 26S proteasome with ubiquitinated substrate
The yeast holoenzyme caught on a substrate, for a species comparison with the human states.

References

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