Cooperativity in Proteasome Core Particle Maturation
Anjana Suppahia,
Pushpa Itagi,
Alicia Burris,
Faith Mi Ge Kim,
Alexander Vontz,
Anupama Kante,
Seonghoon Kim,
Wonpil Im,
Eric J. Deeds,
Jeroen Roelofs
Affiliations
Anjana Suppahia
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA; Molecular, Cellular, and Developmental Biology Program, Division of Biology, Kansas State University, 338 Ackert Hall, Manhattan, KS 66506, USA
Pushpa Itagi
Center for Computational Biology, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA; Institute for Quantitative and Computational Biosciences, University of California Los Angeles, Los Angeles, CA 99024, USA
Alicia Burris
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA; Molecular, Cellular, and Developmental Biology Program, Division of Biology, Kansas State University, 338 Ackert Hall, Manhattan, KS 66506, USA
Faith Mi Ge Kim
Molecular, Cellular, and Developmental Biology Program, Division of Biology, Kansas State University, 338 Ackert Hall, Manhattan, KS 66506, USA
Alexander Vontz
Molecular, Cellular, and Developmental Biology Program, Division of Biology, Kansas State University, 338 Ackert Hall, Manhattan, KS 66506, USA
Anupama Kante
Institute for Quantitative and Computational Biosciences, University of California Los Angeles, Los Angeles, CA 99024, USA; Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66047, USA
Seonghoon Kim
Department of Biological Sciences, Lehigh University, Bethlehem, PA 18105, USA
Wonpil Im
Department of Biological Sciences, Lehigh University, Bethlehem, PA 18105, USA; Department of Bioengineering, Lehigh University, Bethlehem, PA 18105, USA; Department of Chemistry, Lehigh University, Bethlehem, PA 18105, USA
Eric J. Deeds
Center for Computational Biology, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA; Institute for Quantitative and Computational Biosciences, University of California Los Angeles, Los Angeles, CA 99024, USA; Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA 99024, USA; Corresponding author
Jeroen Roelofs
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA; Molecular, Cellular, and Developmental Biology Program, Division of Biology, Kansas State University, 338 Ackert Hall, Manhattan, KS 66506, USA; Corresponding author
Summary: Proteasomes are multi-subunit protease complexes found in all domains of life. The maturation of the core particle (CP), which harbors the active sites, involves dimerization of two half CPs (HPs) and an autocatalytic cleavage that removes β propeptides. How these steps are regulated remains poorly understood. Here, we used the Rhodococcus erythropolis CP to dissect this process in vitro. Our data show that propeptides regulate the dimerization of HPs through flexible loops we identified. Furthermore, N-terminal truncations of the propeptides accelerated HP dimerization and decelerated CP auto-activation. We identified cooperativity in autocatalysis and found that the propeptide can be partially cleaved by adjacent active sites, potentially aiding an otherwise strictly autocatalytic mechanism. We propose that cross-processing during bacterial CP maturation is the underlying mechanism leading to the observed cooperativity of activation. Our work suggests that the bacterial β propeptide plays an unexpected and complex role in regulating dimerization and autocatalytic activation.
