Fig. 1.
Multivalent binding motif by which the bacterial peptide FnBPA5 specifically recognizes the N-terminal fibronectin (Fn) type I domains (FnI). a Schematic representation of the multidomain protein Fn. The binding epitope for FnBPA5 (purple) is located near the N-terminus of fibronectin (gray). b FnBPA5 binds to modules FnI2–5 (white, strands forming intermolecular β-sheets in gray) via an antiparallel beta-zipper by forming an extensive network of backbone hydrogen bonds (orange dotted lines). Linker residues of FnBPA5 that connect the β-strands are shown in darker purple. c Surface rendering of the complex shown in b, highlighting the snug fit of the interaction. Odd-numbered FnI modules are shown in darker gray for distinction. d FnBPA5 binds to relaxed, but not to stretched Fn fibers, as fiber stretching causes a structural mismatch with its multivalent binding epitope located on the Fn type I domains FnI2–5. e Stretching of Fn leads to a reduction of multivalency and thus an affinity switch to low binding of FnBPA5. f Sequences of the FnBPA5 peptide and its randomly scrambled negative control, scraFnBPA5. Residues in the wild type peptide forming intermolecular β-sheets are indicated with light purple arrows, and residues of the scrambled control peptide conserved with respect to the wild type are shown in black. Both peptides were labeled on the N-terminal cysteine residues (yellow) with Alexa488 or Cy5 fluorophores for in vitro experiments and NODAGA for in vivo experiments