Rational design of a non-canonical "sticky-ended" collagen triple helix.
In a canonical collagen triple helix, three peptides self-assemble into a supercoiled motif with a one-amino-acid offset between the peptide chains. Design of triple helices that contain more than one residue offset is lucrative, as it leaves the non-covalent interactions unsatisfied at the termini and renders the termini "sticky" to further self-assemble into collagen-like nanofibers. Here we use lysine-glutamate axial salt-bridges to design a heterotrimeric collagen triple helix, ABC-1, containing a non-canonical offset of four residues between the peptide chains. The four-residue offset is necessary to prevent aggregation, which would prevent characterization of the non-canonical chain arrangement at the molecular level by NMR spectroscopy. A second heterotrimer, ABC-2, also stabilized by axial salt-bridges, is designed containing a canonical one-amino-acid offset to facilitate comparison of structure and stability by CD and NMR. ABC-1 and ABC-2 demonstrate our ability to modulate chain offset in a collagen triple helix. This lays the groundwork to design longer, and therefore stickier, offsets allowing access to a new class of collagen-related nanostructures.
Departments of Chemistry and Bioengineering, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
Abhishek A
AA
Jalan
Katherine A
KA
Jochim
Jeffrey D
JD
Hartgerink
D000595:Amino Acid Sequence; D001672:Biocompatible Materials; D003094:Collagen / Q000737:chemistry*; D008958:Models, Molecular; D057139:Nanofibers; D011487:Protein Conformation
D001672:Biocompatible Materials; D003094:Collagen