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. Author manuscript; available in PMC: 2024 Nov 3.
Published in final edited form as: Cell. 2024 Sep 16;187(22):6200–6219.e23. doi: 10.1016/j.cell.2024.08.036

Figure 7. Dynamic entropy-based allosteric model of TGF-β activation.

Figure 7.

(A) Cartoon of intrinsic and integrin-induced TGF-β1 activation. 1) L-TGF-β1/GARP has relatively low basal entropy in straitjacket/lasso, insufficient to trigger significant signaling. 2) Binding αvβ8 stabilizes arm domain but redistributes sufficient entropy to expose mature TGF-β1 to TGF-βRs to trigger signaling.

(B) Cartoon of intrinsic and integrin-induced TGF-β3 activation. 3) TGF-β3/GARP has relatively high levels of basal entropy in straitjacket/lasso sufficient to expose mature TGF-β3 to TGF-βRs allowing basal L-TGF-β3 constitutive autocrine signaling. 4) Binding to αvβ8 stabilizes the arm domain redistributing entropy exposing mature TGF-β3 to TGF-βRs, sufficient for paracrine release of mature TGF-β3 for bidirectional signaling to L-TGF-β3 presenting, and αvβ8 expressing cells.