Extreme disorder in an ultrahigh-affinity protein complex

Nature
Alessandro BorgiaBenjamin Schuler

Abstract

Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes.

References

Oct 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·J ZarbockA M Gronenborn
May 23, 1994·FEBS Letters·T Papamarcaki, O Tsolas
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Jun 26, 1998·The Biochemical Journal·J Gomez-Marquez, P Rodríguez
Jul 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·B A ShoemakerP G Wolynes
Jan 29, 2002·Journal of Molecular Biology·Kathryn A ScottJane Clarke
Sep 19, 2002·Protein Science : a Publication of the Protein Society·John Karanicolas, Charles L Brooks
Jul 21, 2005·Accounts of Chemical Research·Achillefs N KapanidisShimon Weiss
Aug 23, 2005·Biophysical Journal·Barbara K MüllerDon C Lamb
Nov 23, 2005·The Journal of Biological Chemistry·Jeffrey C HansenRobert W Woody
May 23, 2006·Current Opinion in Structural Biology·Philip J J Robinson, Daniela Rhodes
Oct 3, 2006·Nature Methods·Ivan RasnikTaekjip Ha
Dec 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Armin HoffmannBenjamin Schuler
Feb 3, 2007·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Thomas DertingerJörg Enderlein
Feb 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Daniel NettelsBenjamin Schuler
May 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mikael BorgHue Sun Chan
Jul 31, 2007·Nature Structural & Molecular Biology·Jennifer M R BakerJulie D Forman-Kay
Dec 7, 2007·Trends in Biochemical Sciences·Peter Tompa, Monika Fuxreiter
Dec 18, 2007·Journal of Molecular Biology·Young C Kim, Gerhard Hummer
Nov 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Tanja MittagJulie D Forman-Kay
Jan 23, 2009·Current Opinion in Structural Biology·Peter E Wright, H Jane Dyson
Feb 7, 2009·Chemical Reviews·G SchreiberH-X Zhou
Apr 28, 2009·Journal of the American Chemical Society·Sung-Hun BaePeter E Wright
Sep 11, 2009·The Journal of Chemical Physics·Irina V GopichAttila Szabo
May 4, 2010·FEBS Letters·Eric M George, David T Brown
Jul 16, 2010·Methods in Enzymology·Evangelos SisamakisClaus A M Seidel
Jul 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sonja Müller-SpäthBenjamin Schuler
Sep 8, 2010·Biophysical Journal·Daria V FedyukinaSilvia Cavagnero
Jan 15, 2011·Journal of Biomolecular NMR·Magnus KjaergaardFlemming M Poulsen
Sep 17, 2011·Progress in Nuclear Magnetic Resonance Spectroscopy·Vladislav Yu Orekhov, Victor A Jaravine
Nov 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Atta AhmadErik R P Zuiderweg
Apr 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Andrea SorannoBenjamin Schuler
Sep 18, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hagen HofmannBenjamin Schuler
Nov 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Bing-Rui ZhouYawen Bai
Apr 18, 2014·Chemical Reviews·Johnny HabchiVladimir N Uversky
Aug 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ruth KellnerBenjamin Schuler
Feb 6, 2015·Nature Communications·Stephan BenkeBenjamin Schuler

❮ Previous
Next ❯

Citations

Jun 15, 2018·Proceedings of the National Academy of Sciences of the United States of America·Kristian K KristensenMichael Ploug
Aug 2, 2018·Cellular and Molecular Life Sciences : CMLS·Alexander V FoninVladimir N Uversky
Aug 12, 2018·Protein Science : a Publication of the Protein Society·Hiroki OkazakiHidekazu Hiroaki
Oct 12, 2018·Proceedings of the National Academy of Sciences of the United States of America·Abigail L TurnerKatherine Stott
Aug 24, 2018·Chembiochem : a European Journal of Chemical Biology·Oleta T JohnsonAmanda L Garner
Jul 31, 2018·Protein Science : a Publication of the Protein Society·Yannick MesrouzePatrick Chène
Sep 16, 2018·Proteomics·Prakash Kulkarni, Vladimir N Uversky
Jan 12, 2019·Physical Chemistry Chemical Physics : PCCP·Alexander K FooteRandall H Goldsmith
Feb 7, 2019·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Benjamin CroopKyu Young Han
Nov 6, 2018·Proceedings of the National Academy of Sciences of the United States of America·Eric B Gibbs, Richard W Kriwacki
Feb 23, 2019·Protein Science : a Publication of the Protein Society·Elizabeth M BafaroRobert E Dempski
Apr 14, 2019·Biomolecules·Supriyo Bhattacharya, Xingcheng Lin
Apr 14, 2019·Biomolecules·Prakash Kulkarni, Vladimir N Uversky
May 30, 2019·Future Medicinal Chemistry·Kanin WichapongGerry Af Nicolaes
Jul 13, 2019·Protein Science : a Publication of the Protein Society·Jianhong ZhouA Keith Dunker
May 30, 2019·The Journal of Membrane Biology·Rajeswari AppaduraiAnand Srivastava
Aug 24, 2019·Protein Science : a Publication of the Protein Society·Jing YangYongqi Huang
Jun 4, 2018·Nucleic Acids Research·Bálint MészárosZsuzsanna Dosztányi
Nov 12, 2019·Journal of Biomolecular Structure & Dynamics·Jing YangYongqi Huang
Nov 13, 2019·Nucleic Acids Research·András HatosDamiano Piovesan
Sep 7, 2019·Proceedings of the National Academy of Sciences of the United States of America·Renee VancraenenbroeckHagen Hofmann
Oct 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Charlotte S Sørensen, Magnus Kjaergaard
Oct 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Ben A MeinenJames C A Bardwell
Mar 2, 2018·Nature·Rebecca B Berlow, Peter E Wright
Apr 4, 2020·Physical Chemistry Chemical Physics : PCCP·Irene Ruiz-Ortiz, David De Sancho
Feb 26, 2020·Annual Review of Physical Chemistry·Lauren Ann Metskas, Elizabeth Rhoades
Jun 6, 2019·Nature Communications·Erik D HolmstromBenjamin Schuler
May 27, 2020·PLoS Computational Biology·Attila HorvathMonika Fuxreiter
Aug 25, 2020·Cell Communication and Signaling : CCS·Pernille SeiffertBirthe B Kragelund
Sep 17, 2020·Cellular and Molecular Life Sciences : CMLS·Lasse StabyBirthe B Kragelund
Aug 17, 2018·Optics Express·Yiling SongPeixiang Lu
Nov 11, 2018·Nature Communications·Flurin SturzeneggerBenjamin Schuler
Dec 21, 2018·Biomolecules·Prakash Kulkarni, Vladimir N Uversky
Nov 9, 2018·Proceedings of the National Academy of Sciences of the United States of America·Ang GaoArup K Chakraborty

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.