In:
Acta Crystallographica Section D Structural Biology, International Union of Crystallography (IUCr), Vol. 72, No. 5 ( 2016-05-01), p. 658-674
Abstract:
The cytokine TGF-β modulates a number of cellular activities and plays a critical role in development, hemostasis and physiology, as well as in diseases including cancer and fibrosis. TGF-β signals through two transmembrane serine/threonine kinase receptors: TGFβR1 and TGFβR2. Multiple structures of the TGFβR1 kinase domain are known, but the structure of TGFβR2 remains unreported. Wild-type TGFβR2 kinase domain was refractory to crystallization, leading to the design of two mutated constructs: firstly, a TGFβR1 chimeric protein with seven ATP-site residues mutated to their counterparts in TGFβR2, and secondly, a reduction of surface entropy through mutation of six charged residues on the surface of the TGFβR2 kinase domain to alanines. These yielded apo and inhibitor-bound crystals that diffracted to high resolution ( 〈 2 Å). Comparison of these structures with those of TGFβR1 reveal shared ligand contacts as well as differences in the ATP-binding sites, suggesting strategies for the design of pan and selective TGFβR inhibitors.
Type of Medium:
Online Resource
ISSN:
2059-7983
DOI:
10.1107/S2059798316003624
DOI:
10.1107/S2059798316003624/dw5158sup1.pdf
Language:
Unknown
Publisher:
International Union of Crystallography (IUCr)
Publication Date:
2016
detail.hit.zdb_id:
2968623-4
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