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    Maturation of the proteasome core particle induces an affinity switch that controls regulatory particle association

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    Issue Date
    2015-03-16
    Author
    Wani, Prashant S.
    Rowland, Michael A.
    Ondracek, Alex
    Deeds, Eric J.
    Roelofs, Jeroen
    Publisher
    Nature Publishing Group
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Published Version
    http://www.nature.com/articles/ncomms7384
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    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.
    URI
    http://hdl.handle.net/1808/22589
    DOI
    https://doi.org/10.1038/ncomms7384
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    • Center for Computational Biology Scholarly Works [38]
    Citation
    Wani, Prashant S., Michael A. Rowland, Alex Ondracek, Eric J. Deeds, and Jeroen Roelofs. "Maturation of the Proteasome Core Particle Induces an Affinity Switch That Controls Regulatory Particle Association." Nature Communications 6 (2015): 6384.

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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