Where does pepsin cleave a human type 1 collagen molecule? Does it occur at multiple locations or only one?
There are multiple types of collagen variants, so the answer here is somewhat non-specific. Pepsin is an endo type of serine protease and it has low specificity. Proteolysis depends on residues upstream (P1’) and downstream (P1) of the recognition site. Hydrophobic residues at P1’ and P1 increase the likelihood of successful proteolysis. An aromatic residue such as Phe, Trp and Tyr at P1’ and a hydrophobic residue Phe, Leu and Met at P1 are associated with highest likelihood of successful proteolysis. Positively charged residues such as His, Lys and Arg at position P1 are detrimental to proteolysis. A collagen fiber contains multiple fibrils that are made up of tropocollagen molecules, strengthened by cross-links. Tropocollagen is in fact comprised of three left-handed procollagen molecules, forming a right-handed triple helical structure. Treatment of acid-soluble tropocollagen with pepsin releases multiple peptides whose composition mainly includes Glycine, Tyrosine, Leucine and Phenylalanine amino acids among others.