title: Maturation of the proteasome core particle induces an affinity switch that controls regulatory particle association.
abstract: Proteasome assembly is a complex process, requiring 66 subunits distributed over several subcomplexes to associate in a coordinated fashion. Ten proteasome-specific chaperones have been identified that assist in this process. For two of these, the Pba1-Pba2 dimer, it is well established that they only bind immature core particles (CPs) in vivo. In contrast, the regulatory particle (RP) utilizes the same binding surface but only interacts with the mature CP in vivo. It is unclear how these binding events are regulated. Here, we show that Pba1-Pba2 binds tightly to the immature CP, preventing RP binding. Changes in the CP that occur on maturation significantly reduce its affinity for Pba1-Pba2, enabling the RP to displace the chaperone. Mathematical modelling indicates that this 'affinity switch' mechanism has likely evolved to improve assembly efficiency by preventing the accumulation of stable, non-productive intermediates. Our work thus provides mechanistic insights into a crucial step in proteasome biogenesis.
authors: Graduate Biochemistry Group, Department of Biochemistry and Molecular Biophysics, Kansas State University, 336 Ackert Hall, Manhattan, Kansas 66506, USA.
authors: Prashant S
authors: PS
authors: Wani
authors: Center for Computational Biology, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047, USA.
authors: Michael A
authors: MA
authors: Rowland
authors: Molecular, Cellular and Developmental Biology Program, Division of Biology, Kansas State University, 338 Ackert Hall, Manhattan, Kansas 66506, USA.
authors: Alex
authors: A
authors: Ondracek
authors: 1] Center for Computational Biology, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047, USA [2] Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66047, USA [3] Santa Fe Institute, Santa Fe, New Mexico 87501, USA.
authors: Eric J
authors: EJ
authors: Deeds
authors: 1] Graduate Biochemistry Group, Department of Biochemistry and Molecular Biophysics, Kansas State University, 336 Ackert Hall, Manhattan, Kansas 66506, USA [2] Molecular, Cellular and Developmental Biology Program, Division of Biology, Kansas State University, 338 Ackert Hall, Manhattan, Kansas 66506, USA.
authors: Jeroen
authors: 0000000309442465
authors: J
authors: Roelofs
mesh_terms: D015180:Electrophoresis, Gel, Two-Dimensional; D008958:Models, Molecular; D008962:Models, Theoretical; D018832:Molecular Chaperones / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D018832:Molecular Chaperones; C559194:Pba1 protein, S cerevisiae; C559196:Pba2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex