ABSTRACT The amino acid sequence of the heavy chain of Bombyx mori silk fibroin was derived fromthe gene sequence. The 5, 263-residue (391-kDa) polypeptide chain comprises 12 low-complexity "crystalline" domains made up of Gly-X repeats and covering 94% of the sequence; Xis Ala in 65%, Ser in 23%, and Tyr in 9% of the repeats. The remainder includes a nonrepetitive 151-residue header sequence, 11 nearly identical copies of a 43-residue spacer sequence, and a 58-residue C-terminal sequence. The header sequence is homologous to the N-terminal sequence of other fibroins with a completely different crystalline region. In Bombyx mori, each crystalline domain is made up of subdomains of; 70 residues, which in most cases begin with repeats of the GAGAGS hexapeptide and terminate with the GAAS tetrapeptide. Within the subdomains, the Gly-Xalternance is strict, whichstrongly supports the classic Pauling-Corey model, in which b-sheets pack on each other in alternating layers of Gly/Gly and X/X contacts. When fitting the actual sequence tothat model, we propose that eachsubdomain forms a b-strand and each crystalline domain a two-layered b-sandwich, and we suggest that the b-sheets may be parallel, rather thanantiparallel, as hasbeenassumeduptonow. Proteins 2001; 44: 119-122.