The disordered PCI-binding human proteins CSNAP and DSS1 have diverged in structure and function

January 5, 2022

Title

The disordered PCI-binding human proteins CSNAP and DSS1 have diverged in structure and function

Author

Sarah F. Ruidiaz, Jesper E. Dreier, Rasmus Hartmann-Petersen, Birthe B. Kragelund

Year

2021

Journal

PROTEIN SCIENCE

Abstract

Intrinsically disordered proteins (IDPs) regularly constitute components of larger protein assemblies contributing to architectural stability. Two small, highly acidic IDPs have been linked to the so-called PCI complexes carrying PCI-domain subunits, including the proteasome lid and the COP9 signalosome. These two IDPs, DSS1 and CSNAP, have been proposed to have similar structural propensities and functions, but they display differences in their interactions and interactome sizes. Here we characterized the structural properties of human DSS1 and CSNAP at the residue level using NMR spectroscopy and probed their propensities to bind ubiquitin. We find that distinct structural features present in DSS1 are completely absent in CSNAP, and vice versa, with lack of relevant ubiquitin binding to CSNAP, suggesting the two proteins to have diverged in both structure and function. Our work additionally highlights that different local features of seemingly similar IDPs, even subtle sequence variance, may endow them with different functional traits. Such traits may underlie their potential to engage in multiple interactions thereby impacting their interactome sizes.

Instrument

J-810

Keywords

IDPs, Intrinsically disordered proteins, DSS1, CSNAP, interactions