(Top) Close-up model view of the native (left, Gly562) or mutant (right, Arg562) A subunit. The tertiary structure of the normal A subunit is based on x-ray diffraction analysis.30 The main chain of the protein is drawn as an A carbon trace. Side chain groups of labeled residues are shown as ball-and-stick structures. Although the mutant Arg562 residue can be accommodated by the chemical structure, it generates unfavorable short contacts with neighboring residues. Accordingly, the substitution of a small residue by a large charged amino acid is expected to yield an unstable, misfolded structure. (Bottom left) Model view for the A subunit dimer including the normal domain II, the first half of domain III, the second half of domain III in a monomer, and the same domains II and III in the counterpart monomer. Domains IV and V are not shown. A total of 268 residues consisting of the second half of domain III and domains IV and V are removed from the molecule in the deletion mutant of case no. 1. The C-terminal Leu463 residue of the truncated molecule is shown. Pro383 and Asp384 residues contact with the second part of domain III, which is absent in the mutant. (Bottom right) Closer view of the environment around domains II and III. Because premature termination at position 464 would lead to the loss of a C-terminal part of the core domain and the entire domains IV and V (barrel 1 and 2), the protein is expected to misfold and/or be incapable of dimer formation.