Multiple fuzzy interactions in the moonlighting function of thymosin-β4

Intrinsically Disordered Proteins
Agnes TantosPeter Tompa

Abstract

Thymosine β4 (Tß4) is a 43 amino acid long intrinsically disordered protein (IDP), which was initially identified as an actin-binding and sequestering molecule. Later it was described to have multiple other functions, such as regulation of endothelial cell differentiation, blood vessel formation, wound repair, cardiac cell migration, and survival.(1) The various functions of Tβ4 are mediated by interactions with distinct and structurally unrelated partners, such as PINCH, ILK, and stabilin-2, besides the originally identified G-actin. Although the cellular readout of these interactions and the formation of these complexes have been thoroughly described, no attempt was made to study these interactions in detail, and to elucidate the thermodynamic, kinetic, and structural underpinning of this range of moonlighting functions. Because Tβ4 is mostly disordered, and its 4 described partners are structurally unrelated (the CTD of stabilin-2 is actually fully disordered), it occurred to us that this system might be ideal to characterize the structural adaptability and ensuing moonlighting functions of IDPs. Unexpectedly, we found that Tβ4 engages in multiple weak, transient, and fuzzy interactions, i.e., it is capable of mediating dist...Continue Reading

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Citations

Dec 24, 2017·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Mónika BokorKálmán Tompa
May 30, 2020·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·M BokorK Tompa
Aug 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Haipeng Liu, Constance J Jeffery
Feb 24, 2021·Journal of Proteome Research·Mónika Bokor, Ágnes Tantos
Mar 31, 2021·The Journal of Clinical Investigation·Sonali MunshawNicola Smart

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Methods Mentioned

BETA
co-immunoprecipitation
Fluorescence
NMR
X-ray
gel filtration

Software Mentioned

ANCHOR
TopSpin
Octet
Origin ( MicroCal )
CDPro

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