Disorder in a target for the smad2 mad homology 2 domain and its implications for binding and specificity.

The Journal of Biological Chemistry
P A ChongJulie D Forman-Kay

Abstract

The Smad2 Mad homology 2 (MH2) domain binds to a diverse group of proteins which do not share a common sequence motif. We have used NMR to investigate the structure of one of these interacting proteins, the Smad binding domain (SBD) of Smad anchor for receptor activation (SARA). Our results indicate that the unbound SBD is highly disordered and forms no stable secondary or tertiary structures. Additionally we have used fluorescence binding studies to study the interaction between the MH2 domain and SBD and find that no region of the SBD dominates the interaction between the MH2 and the SBD. Our results are consistent with a series of hydrophobic patches on the MH2 that are able to recognize disordered regions of proteins. These findings elucidate a mechanism by which a single domain (MH2) can specifically recognize a diverse set of proteins which are unrelated by sequence, lead to a clearer picture of how MH2 domains function in the transforming growth factor-beta-signaling pathway and suggest possible mechanisms for controlling interactions with MH2 domains.

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Citations

Oct 13, 2010·Proceedings of the National Academy of Sciences of the United States of America·P Andrew ChongJulie D Forman-Kay
Jul 9, 2009·Journal of Molecular Recognition : JMR·Tanja MittagJulie D Forman-Kay
Jan 23, 2009·Current Opinion in Structural Biology·Peter E Wright, H Jane Dyson
Jan 19, 2018·Annual Review of Biophysics·Alex S Holehouse, Rohit V Pappu
Dec 1, 2017·Cell Communication and Signaling : CCS·Eva María García-VizcaínoFrancisco José Nicolás
Apr 28, 2006·The Journal of Biological Chemistry·P Andrew ChongJulie D Forman-Kay
Jun 9, 2021·The Biochemical Journal·Kaare TeilumBirthe B Kragelund

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