Cd-metallothionein-a test object for dark-field studies of protein structure.

Cadmium-metallothionein contains about six metal atoms per 6,000 molecular weight, reflecting the high proportion of cystein residues in the structure. Because of the strong scattering from probable Cd-S (Cyst)3 complexes, the protein is unambiguously visualized by conventional tilted beam dark-field electronmicroscopy. The projections of the structure correspond to free, aggregated and partially denatured forms of the presumed native structure, a hexahedral mass, 36 multiplied by 25 multiplied by 16 A. Relaxed states of this structure show that the molecule is comprised of two similar, covalently linked "half-metallothineins", each comprised of three domains. Each of the six domains of the native structure is evidently formed by stacking of two characteristic scattering centers together, at a separation of 9 A. A speculative scheme for the folding of the native structure is presented. The results are interpreted as substantiating the fidelity of dark-field images of small proteins, and the cadmium-metallothionein molecule is suggested as a standard test object for the method.