Dynamics-modulated biological activity of transforming growth factor beta3.
Transforming growth factor beta3 (TGF-beta3) is an important mediator of growth, maintenance, and repair processes in human cells. Internal dynamic properties have been derived from (15)N NMR relaxation data and mapped onto the spatial structure of TGF-beta3. The pattern of internal dynamics in the structure identifies potential "hot spots" of binding free energy and reveals the importance of conformational entropy in the interaction of TGF-beta3 with the receptors. The observed internal dynamics set TGF-beta3 apart from other TGF-beta isoforms, with which it shares the same fold. These findings may explain functional differences among the various TGF-beta isoforms and thus prove essential in the search for related therapeutic agents.
Bocharov
Eduard V
EV
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya, 16/10, Moscow 117997, Russia.
Korzhnev
Dmitry M
DM
Blommers
Marcel J J
MJ
Arvinte
Tudor
T
Orekhov
Vladislav Yu
VY
Billeter
Martin
M
Arseniev
Alexander S
AS
D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011509:Proteoglycans / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism*; D053782:Transforming Growth Factor beta3
D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; C071736:betaglycan