Sequence-to-Conformation Relationships of Disordered Regions Tethered to Folded Domains of Proteins

Journal of Molecular Biology
Anuradha MittalRohit V Pappu

Abstract

Intrinsically disordered proteins and regions (IDPs/IDRs) are characterized by well-defined sequence-to-conformation relationships (SCRs). These relationships refer to the sequence-specific preferences for average sizes, shapes, residue-specific secondary structure propensities, and amplitudes of multiscale conformational fluctuations. SCRs are discerned from the sequence-specific conformational ensembles of IDPs. A vast majority of IDPs are actually tethered to folded domains (FDs). This raises the question of whether or not SCRs inferred for IDPs are applicable to IDRs tethered to FDs. Here, we use atomistic simulations based on a well-established forcefield paradigm and an enhanced sampling method to obtain comparative assessments of SCRs for 13 archetypal IDRs modeled as autonomous units, as C-terminal tails connected to FDs, and as linkers between pairs of FDs. Our studies uncover a set of general observations regarding context-independent versus context-dependent SCRs of IDRs. SCRs are minimally perturbed upon tethering to FDs if the IDRs are deficient in charged residues and for polyampholytic IDRs where the oppositely charged residues within the sequence of the IDR are separated into distinct blocks. In contrast, the in...Continue Reading

References

May 5, 1982·Journal of Molecular Biology·J Kyte, R F Doolittle
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Nov 5, 1999·Journal of Molecular Biology·P E Wright, H J Dyson
Aug 10, 2000·Nature Structural Biology·S RaghunathanG Waksman
May 31, 2001·Journal of Molecular Graphics & Modelling·A K DunkerZ Obradovic
Sep 5, 2001·Nature Biotechnology·A K Dunker, Z Obradovic
Mar 23, 2002·Protein Science : a Publication of the Protein Society·Vladimir N Uversky
May 23, 2002·Biochemistry·A Keith DunkerZoran Obradović
Jun 14, 2003·Science·Cyrus ChothiaSarah A Teichmann
Jul 31, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Peter Tompa, Peter Csermely
Mar 2, 2005·Nature Reviews. Molecular Cell Biology·H Jane Dyson, Peter E Wright
Jan 24, 2008·Molecular and Cellular Biology·Ivan M BlasutigTony Pawson
Apr 23, 2008·Bioinformatics·Takashi Ishida, Kengo Kinoshita
May 29, 2008·Journal of Computational Chemistry·Andreas Vitalis, Rohit V Pappu
Jul 18, 2009·Journal of Molecular Biology·Xiang ChenKylie J Walters
Apr 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Albert H MaoRohit V Pappu
Jan 1, 2009·Annual Reports in Computational Chemistry·Andreas Vitalis, Rohit V Pappu
May 21, 2010·Biophysical Journal·Joseph A Marsh, Julie D Forman-Kay
May 21, 2010·Nature Reviews. Molecular Cell Biology·Wendell A Lim
Jul 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sonja Müller-SpäthBenjamin Schuler
Jul 12, 2011·Structure·Buyong MaRuth Nussinov
Nov 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·Faruck MorcosMartin Weigt
Apr 13, 2012·PloS One·Rita Pancsa, Peter Tompa
Jun 19, 2012·Journal of Biomolecular Structure & Dynamics·Bin XueVladimir N Uversky
Sep 22, 2012·Science·M Madan BabuRohit V Pappu
Dec 18, 2012·The Biochemical Journal·Albert H MaoRohit V Pappu
Aug 1, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rahul K Das, Rohit V Pappu
Oct 5, 2013·The Journal of Chemical Physics·Nicholas LyleRohit V Pappu
Nov 30, 2013·Nucleic Acids Research·Robert D FinnMarco Punta
Mar 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Diana M MitreaRichard W Kriwacki
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·René WuttkeBenjamin Schuler
Apr 18, 2014·Nature·Hesam N MotlaghVincent J Hilser
Apr 30, 2014·Chemical Reviews·Robin van der LeeM Madan Babu
Oct 12, 2014·Seminars in Cell & Developmental Biology·P J BuskePetra Anne Levin
Dec 23, 2014·Nature Reviews. Molecular Cell Biology·Peter E Wright, H Jane Dyson
Apr 13, 2015·Current Opinion in Structural Biology·Rahul K DasRohit V Pappu

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Citations

Jan 31, 2019·Briefings in Bioinformatics·Pablo MierMiguel A Andrade-Navarro
Apr 2, 2019·The FEBS Journal·Frank Gondelaud, Sylvie Ricard-Blum
Jan 9, 2019·Cold Spring Harbor Perspectives in Biology·Titus M Franzmann, Simon Alberti
Oct 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Charlotte S Sørensen, Magnus Kjaergaard
Feb 26, 2020·Annual Review of Physical Chemistry·Lauren Ann Metskas, Elizabeth Rhoades
Aug 21, 2020·Proceedings of the National Academy of Sciences of the United States of America·Mateusz Dyla, Magnus Kjaergaard
Sep 17, 2020·Cellular and Molecular Life Sciences : CMLS·Lasse StabyBirthe B Kragelund
Aug 4, 2019·Protein Engineering, Design & Selection : PEDS·Megan C CohanRohit V Pappu
Oct 30, 2019·Scientific Reports·Albert Perez-RibaLaura S Itzhaki
Jul 28, 2019·Nature Communications·Wenqin BaiFuzhong Zhang
Dec 15, 2020·Journal of Molecular Biology·Nicolas PalopoliGustavo Parisi
Feb 14, 2021·Biophysical Chemistry·Richard J LindsayTongye Shen
Feb 21, 2019·Developmental Cell·Kristina N Schaefer, Mark Peifer
Dec 19, 2018·Journal of Molecular Biology·Ranajeet Ghose
Jul 22, 2021·Computational and Structural Biotechnology Journal·Ilinka ClercJuan Cortés
Jul 14, 2021·Accounts of Chemical Research·Jacque L FayloDavid W Christianson
Aug 22, 2021·Journal of Molecular Biology·Kiersten M Ruff, Rohit V Pappu
Oct 14, 2021·Journal of Chemical Theory and Computation·João MoradoChris-Kriton Skylaris
Dec 7, 2021·The Journal of Physical Chemistry. B·Galo E BalattiSebastian Fernandez-Alberti

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