Comparison of frozen-hydrated and negatively stained crystals of Ca-ATPase suggests a shape for the intramembranous domain.

generated depends upon some physical property such as mass or refractive index of the partner from the bulk phase. Since the transducer responds only to changes at its surface, bulk-phase interference can be eliminated. Probes such as fluorescent labels are not required. Of the various biosensor technologies that are suitable for this purpose, surface plasmon resonance (s.p.r.) methods are currently the most advanced [S-71. S.p.r. methods enable the kinetics of macromolecular binding or disassociation to be measured in real time at a resolution of 1 s or so, in a volume of 100 pI or less, at a sensitivity of less than a few femtomoles of ligand bound/ mm? of surface. The choice of binding pairs is very wide. Irrespective of the value of s.p.r. technology for commercial diagnostics, it is likely to become a technique of considerable value to the research biochemist or molecular biologist. I . Garland, P. B. & Birmingham, J. J. (1986) in Applit~utions of I.‘luore.sc~ence in /he Hiomediccrl Scicwces (Taylor. D. L.. Lanni, F. & Waggoner, A. L., eds.), pp. 245-254, Alan Liss Inc., New York 2. Cherry, R. J. ( 1 979) Hiochem. Hiophys. Act0 559,289-327 3. Sheetz. M. P., Turney. S., Qian, H. & Elson, E. L. ( 1 989) Ncrtirrc