A Lateral Salt Bridge for the Specific Assembly of an ABC-Type Collagen Heterotrimer

Abstract

Nature uses salt bridges to control the folding and stability of many proteins, including collagen, the key structural protein in mammals. Here, we present an interstrand salt bridge between (4<i>S</i>)-aminoproline (Amp) and aspartic acid (Asp) that directs the composition and register-specific assembly of synthetic collagen heterotrimers. This Amp-Asp salt bridge allowed for the rational design of strands that fold into A₂B and ABC-type heterotrimers with only three salt bridges per triple helix. Native ESI-MS and NMR spectroscopic analyses corroborated the specific assembly of the ABC heterotrimer.