Mechanical Transition from α-Helical Coiled Coils to ss-Sheets in Fibrin(ogen)

摘要

We characterized the α-to-β transition in α-helical coiled-coil connectors of the human fibrin (ogen) molecule using biomolecular simulations of their forced elongation and theoretical modeling. The force (F)-extension (X) profiles show three distinct regimes: (1) the elastic regime,in which the coiled coils act as entropic springs (F < 100-125 pN; X < 7-8 nm); (2) the constant-force plastic regime,characterized by a force-plateau (F≈150 pN; X≈10-35 nm); and (3) the nonlinear regime (F > 175-200 pN; X >40-50 nm). In the plastic regime, the three-stranded a-helices undergo a noncooperative phase transition to form parallel three-stranded β-sheets. The critical extension of the a-helices is 0.25 nm, and the energy difference between the a-helices and β-sheets is 4.9 kcal/mol per helical pitch. The soft α-to-β phase transition in coiled coils might be a universal mechanism underlying mechanical properties of filamentous α-helical proteins.