麻省理工大学：《生物材料的分子结构》教学讲义（英文版）Molecular switches in the cell

Molecular switches in the cell: fibronectin as a mechanical switch (vogel, 2002) Fibronectin is an adhesion protein secreted by cells and assembled into fibrils to support adhesion and migration Composed of" of fibronectin repeats Fnl, Fnll, and Fnlll connected by short linkers of varying flexibility One particular Fnlll repeat, Fnlll10, contains the RGD amino acid sequence Fnlll modules have interesting force-responsive properties o undergo partial unfolding in response to physiological forces(Figure shows stretched FN repeats in fibrillar FN) integrins bind to and pull on FN fibers through the cytoskeleton o Several potential roles for this sensitivity Expose buried recognition sites So-called sites in Fnllll, Fnlll7-8, Fnlll1o, and FnIlll4 Change relative distance between synergistic binding sites on 2 different modules E. g RGD synergy site between Fnlllg and Fnlll1o Mechanical deformation and straightening of recognition sites on

Molecular switches in the cell: fibronectin as a mechanical switch (Vogel, 2002) ƒ Fibronectin is an adhesion protein secreted by cells and assembled into fibrils to support adhesion and migration ƒ Composed of ‘modules’ of fibronectin repeats FnI, FnII, and FnIII connected by short linkers of varying flexibility ƒ One particular FnIII repeat, FnIII10, contains the RGD amino acid sequence ƒ FnIII modules have interesting force-responsive properties o undergo partial unfolding in response to physiological forces (Figure shows stretched FN repeats in fibrillar FN) ƒ integrins bind to and pull on FN fibers through the cytoskeleton o Several potential roles for this sensitivity: ƒ Expose buried recognition sites x So-called ‘cryptic’ sites in FnIII1, FnIII7-8, FnIII10, and FnIIII14 ƒ Change relative distance between synergistic binding sites on 2 different modules x E.g. RGD synergy site between FnIII9 and FnIII10 ƒ Mechanical deformation and straightening of recognition sites on loops

Structure of fibronectin a Intermediale stale of Fnlll,as under tension (Vogel, 2002) Red- Green e extended Figwe 3: Translating structm changes wthn a potein Other examples of molecular switches in biology Adhesin adhesion protein in E Coli: Anchor to Binding

Structure of fibronectin (Vogel, 2002) Other examples of molecular switches in biology Adhesin adhesion protein in E. Coli: