Structural Insights from X-Ray Crystallography

X-ray crystallography, a robust experimental technique utilizing X-ray diffraction features of crystals, plays a pivotal role in determining precise molecular structures. Despite the inherent challenge of obtaining high-resolution structural information due to collagen's noncrystallizable nature, collagen mimetic peptides have transformed our understanding of collagen's biophysical properties by providing single crystals, stable triple helix structures, well-defined thermal transitions, and precise control of length and chemical composition, facilitating significant breakthroughs. Dozens of collagen mimetic peptides have been resolved with crystal structures at atomic or near-atomic resolution, confirming collagen's essential triple helical features. The crystal structure of T3-785 provides insights into sequence-dependent conformational variations in the triple-helical structure, while the integrin-binding peptide GFOGER reveals significant conformational changes between unliganded and ligand-bound forms. This chapter also explores crystal structures of Gly substitutions and natural interruptions, revealing differences in hydration and hydrogen bonding. Furthermore, it investigates crystal structures of heterotrimeric collagen mimic peptides, including both AAB-type and ABC-type heterotrimers, enriching our comprehension of collagen's intricate architecture.