PDBsum entry 1g0u

Hydrolase

PDB id: 1g0u

Contents

Protein chains

246 a.a. *

235 a.a. *

238 a.a. *

230 a.a. *

230 a.a. *

242 a.a. *

240 a.a. *

222 a.a. *

204 a.a. *

198 a.a. *

212 a.a. *

222 a.a. *

233 a.a. *

196 a.a. *

Metals

_MG ×20

Waters ×2908

* Residue conservation analysis

References listed in PDB file

Key reference

Title

A gated channel into the proteasome core particle.

Authors

M.Groll, M.Bajorek, A.Köhler, L.Moroder, D.M.Rubin, R.Huber, M.H.Glickman, D.Finley.

Ref.

Nat Struct Biol, 2000, 7, 1062-1067. [DOI no: 10.1038/80992]

PubMed id

11062564

Abstract

The core particle (CP) of the yeast proteasome is composed of four heptameric rings of subunits arranged in a hollow, barrel-like structure. We report that the CP is autoinhibited by the N-terminal tails of the outer (alpha) ring subunits. Crystallographic analysis showed that deletion of the tail of the alpha 3-subunit opens a channel into the proteolytically active interior chamber of the CP, thus derepressing peptide hydrolysis. In the latent state of the particle, the tails prevent substrate entry by imposing topological closure on the CP. Inhibition by the alpha-subunit tails is relieved upon binding of the regulatory particle to the CP to form the proteasome holoenzyme.

Figure 4.
Figure 4. Contacts among residues of the YDR element in adjacent tails. Detail of the CP channel in the closed state, showing that the carboxylate group of Asp 9 in 3 forms a salt bridge with the guanidinium group of Arg 10 in 4, and a hydrogen bond with the hydroxyl group of Tyr 8 in 4. The carboxylate group of Asp 9 also forms hydrogen bonds with the 3 main chain, as shown.

Figure 5.
Figure 5. Model for coupled regulation of proteasome assembly and inhibition. Proposed late steps in the assembly of the proteasome are depicted. The inhibitory N-terminal sequences of the -subunits and -subunits are represented in red. In the inactive half-CP, inhibition is provided by the -subunit propeptides (which directly block the proteolytic active sites). Inhibition by the -subunit tails becomes effective only when the half-CPs condense to form a closed chamber. The inactive CP is converted to the latent form upon autolysis of the -propeptides. The last step represents holoenzyme formation, which is accompanied by channel opening. For details, see the text. RP, regulatory particle. The schematic representation of -propeptide-mediated inhibition is modified from ref. 20.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 1062-1067) copyright 2000.