Fig. 2.   Structure of the Flu-TTR complex. Ribbon diagram of tetrameric TTR with Flu as computed with the program SETOR (32). The two molecules of Flu, binding into the T4-binding channels of TTR, are shown as a stick model. Because of the twofold axes along the binding channel (pointing from left to right in the paper plane) a second symmetry-related binding mode is present for both molecules (statistic disorder). For clarity, a second molecular conformation of the Flu that is also in agreement with the crystallographic data is not displayed. Each monomer of TTR consists of 127 amino acid residues that form two stacked sheets, each containing four antiparallel -strands (sheet I: HGAD; sheet II: FEBC). The subunits are linked by hydrogen bonds within the -strands H and F with the equivalent strands H' and F' in the second subunit. These interactions extend the two four-stranded -sheets into eight-stranded -sheets in the dimer. Two of these dimers are sandwiched on top of one another to assemble the tetrameric molecule through interactions of the AB and GH loops. The opposition of the convex faces of the -sheets I and I' (because of the right-hand twist of their -strands) gives the funnel-like depressions, representing the two Flu-binding channels.