Dynamic Protein Interaction Networks and New Structural Paradigms in Signaling

Chemical Reviews
Veronika CsizmokJulie D Forman-Kay


Understanding signaling and other complex biological processes requires elucidating the critical roles of intrinsically disordered proteins (IDPs) and regions (IDRs), which represent ∼30% of the proteome and enable unique regulatory mechanisms. In this review, we describe the structural heterogeneity of disordered proteins that underpins these mechanisms and the latest progress in obtaining structural descriptions of conformational ensembles of disordered proteins that are needed for linking structure and dynamics to function. We describe the diverse interactions of IDPs that can have unusual characteristics such as "ultrasensitivity" and "regulated folding and unfolding". We also summarize the mounting data showing that large-scale assembly and protein phase separation occurs within a variety of signaling complexes and cellular structures. In addition, we discuss efforts to therapeutically target disordered proteins with small molecules. Overall, we interpret the remodeling of disordered state ensembles due to binding and post-translational modifications within an expanded framework for allostery that provides significant insights into how disordered proteins transmit biological information.


Jan 1, 1992·Annual Review of Cell Biology·D J Forbes
Dec 13, 1991·Science·H FrauenfelderP G Wolynes
Feb 1, 1987·The Journal of Cell Biology·D R FinlayD J Forbes
Oct 11, 1967·Biochemical and Biophysical Research Communications·W K Paik, S Kim
Nov 15, 1995·Genes & Development·I M VermaS Miyamoto
Jan 1, 1994·Annual Review of Immunology·P A Baeuerle, T Henkel
Dec 16, 1993·Nature·Y XiongD Beach
Jul 1, 1993·Genes & Development·M L ScottD Baltimore
Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·K BrownU Siebenlist
Jun 7, 1996·Biochimica Et Biophysica Acta·M T Brown, J A Cooper
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·R W KriwackiPeter E Wright
Jan 1, 1997·Nature Structural Biology·K A Dill, Hue Sun Chan
Jan 1, 1996·Folding & Design·L J SmithChristopher M Dobson
Feb 7, 1998·European Journal of Biochemistry·B VrhovskiA S Weiss
Jan 1, 1997·Annual Review of Cell and Developmental Biology·S M Thomas, J S Brugge
Apr 30, 1998·Current Opinion in Cell Biology·N Sonenberg, A C Gingras
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·T KamijoC J Sherr
Jul 23, 1998·Critical Reviews in Biochemistry and Molecular Biology·P Van den SteenG Opdenakker
Jul 31, 1998·Protein Science : a Publication of the Protein Society·C M Fletcher, G Wagner
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·B A SchulmanE Harlow
Dec 29, 1998·Cell·M D Jacobs, S C Harrison
Jun 11, 1999·Genes & Development·A C GingrasN Sonenberg
Jul 1, 1999·Protein Science : a Publication of the Protein Society·K A Dill
Aug 24, 1999·Pharmacology & Therapeutics·J D Graves, E G Krebs


Jul 9, 2016·Journal of the American Chemical Society·Asmit BhowmickTeresa Head-Gordon
Sep 8, 2016·Expert Review of Proteomics·Elena L RudashevskayaStavroula Markoutsa
Oct 30, 2016·Current Opinion in Structural Biology·Tiago N CordeiroPau Bernadó
May 23, 2017·Physical Chemistry Chemical Physics : PCCP·Jie HuZhuqing Zhang
Jan 31, 2017·Nature Communications·Shiqian QiJames H Hurley
Jun 21, 2017·Cellular and Molecular Life Sciences : CMLS·Gabriella T HellerMichele Vendruscolo
Mar 15, 2018·Physical Chemistry Chemical Physics : PCCP·Yanhua OuyangZhuqing Zhang
Oct 27, 2017·Proteomics·April L DarlingVladimir N Uversky
Feb 23, 2019·Protein Science : a Publication of the Protein Society·Elizabeth M BafaroRobert E Dempski
Feb 22, 2018·Nature·Alessandro BorgiaBenjamin Schuler
Oct 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Kathryn P SherryDoug Barrick
Sep 7, 2019·Proceedings of the National Academy of Sciences of the United States of America·Renee VancraenenbroeckHagen Hofmann
Nov 23, 2019·Biochemical Society Transactions·Cristina Daneri-BecerraMario D Galigniana
Nov 19, 2019·Proteomics·Gregory TomblineVera Gorbunova
Sep 21, 2018·Proceedings of the National Academy of Sciences of the United States of America·Ke YangPeter E Wright
Sep 26, 2018·Intrinsically Disordered Proteins·Vladimir N Uversky
Sep 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vladimir N Uversky
Aug 4, 2019·Protein Engineering, Design & Selection : PEDS·Megan C CohanRohit V Pappu
Apr 17, 2020·Frontiers in Cell and Developmental Biology·Wenchen PuYong Peng
Jan 16, 2020·Nature Communications·Matthew R King, Sabine Petry
Jun 10, 2017·Cellular and Molecular Life Sciences : CMLS·Ruth NussinovJian Zhang
Aug 22, 2018·Nature Structural & Molecular Biology·Marc BoehningMarkus Zweckstetter
Mar 20, 2020·Nature Catalysis·Bas J H M RosierTom F A de Greef
Jun 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Franziska ZoselBenjamin Schuler
Nov 6, 2020·Science Advances·Gabriella T HellerMichele Vendruscolo
Nov 28, 2020·Molecules and Cells·Sunghyun HongJunseock Koh
Jan 9, 2021·Cancer Cell·Ann BoijaRichard A Young
Dec 25, 2019·Archives of Biochemistry and Biophysics·Alejandra A CovarrubiasDavid F Rendón-Luna
Dec 30, 2020·International Journal of Molecular Sciences·Edoardo SalladiniKaren Skriver
Aug 30, 2017·Biochimica Et Biophysica Acta. General Subjects·Teppei IkeyaChristian Griesinger
Mar 20, 2018·Progress in Nuclear Magnetic Resonance Spectroscopy·Binyong Liang, Lukas K Tamm
Dec 19, 2016·Current Opinion in Structural Biology·Zachary A Levine, Joan-Emma Shea

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