Structural diversity in free and bound states of intrinsically disordered protein phosphatase 1 regulators

Joseph A Marsh, Barbara Dancheck, Michael J Ragusa, Marc Allaire, Julie D Forman-Kay, Wolfgang Peti

Research output: Contribution to journalArticlepeer-review


Complete folding is not a prerequisite for protein function, as disordered and partially folded states of proteins frequently perform essential biological functions. In order to understand their functions at the molecular level, we utilized diverse experimental measurements to calculate ensemble models of three nonhomologous, intrinsically disordered proteins: I-2, spinophilin, and DARPP-32, which bind to and regulate protein phosphatase 1 (PP1). The models demonstrate that these proteins have dissimilar propensities for secondary and tertiary structure in their unbound forms. Direct comparison of these ensemble models with recently determined PP1 complex structures suggests a significant role for transient, preformed structure in the interactions of these proteins with PP1. Finally, we generated an ensemble model of partially disordered I-2 bound to PP1 that provides insight into the relationship between flexibility and biological function in this dynamic complex.
Original languageEnglish
Pages (from-to)1094-103
Number of pages10
Issue number9
Publication statusPublished - 8 Sep 2010


  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Microfilament Proteins
  • Models, Molecular
  • Nerve Tissue Proteins
  • Protein Conformation
  • Protein Folding
  • Protein Phosphatase 1
  • Proteins
  • Structure-Activity Relationship

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