The Scripps Research Institute
La Jolla, CA
Intrinsically Disordered Proteins – Vital Peptide Cogs in Metabolic Machines
Disordered proteins and disordered segments of larger proteins play a vital role in protein-protein interactions in many different metabolic processes. Cellular signaling is vitally dependent on the presence of disorder in the interacting proteins1 – the same polypeptide can make interactions with many partners, leading to pathway cross-talk, and combinatorial post-translational modifications turn signals on and off.
We study disordered proteins and their interactions in solution, primarily using NMR spectroscopy. Our interest has been in the molecular basis of the interactions and the mechanisms by which cellular signaling is controlled. Signaling pathways such as the hypoxia response2 and the role of viral oncoproteins in virus-induced oncogenesis3, 4 are examples that show the central importance of disorder in cellular signaling pathways.
AuthorsH. Jane Dyson and Peter E. Wright
AffiliationsDepartment of Integrative Structural and Computational Biology, Scripps Research, 10550 North Torrey Pines Road, La Jolla CA 92037
1 Intrinsically disordered proteins in cellular signalling and regulation. P.E. Wright and H.J. Dyson, Nat. Rev. Mol. Cell Biol., 2015, 16, 18-29
2 Hypersensitive termination of the hypoxic response by a disordered protein switch. R.B. Berlow, H.J. Dyson and P.E. Wright, Nature 543, 2017, 447-451
3 The high-risk HPV16 E7 oncoprotein mediates interaction between the transcriptional coactivator CBP and the retinoblastoma protein pRb. A.L. Jansma, M.A. Martinez-Yamout, R. Liao, P. Sun, H.J. Dyson and P.E. Wright, J. Mol. Biol., 2014, 426, 4030-4048
4 Structural basis for cooperative regulation of KIX-mediated transcription pathways by the HTLV1 HBZ activation domain. K. Yang, R.L. Stanfield, M.A. Martinez-Yamout, H.J. Dyson and P.E. Wright, Proc. Natl. Acad. Sci. USA, 2018, 115, 10040-10045