Location of constitutive mutations in the extracellular domain 4, transmembrane domain, and cytoplasmic domain of hβc. Determination of a molecular model of domain 4 of hβc has been described previously.28 The transmembrane sequence of hβc was joined manually and an Indigo2 computer (Silicon Graphics, Mountain View, CA) was used to run the molecular modelling programs Insight II and Discover (Molecular Simulations Inc, San Diego, CA). Manual and automated methods were used to select an appropriate -helical conformation for the transmembrane region, and the model was evaluated for stereochemical parameters. The model of the hβc domain 4 and transmembrane domain is presented in cartoon form, using Molscript74 and Raster3D.75 β-strands are indicated by arrowed ribbons and italicized letters. The cytoplasmic domain is depicted in an arbitrary conformation and is shown only to illustrate the location of cytoplasmic mutations. -Carbon atoms of residues targetted for constitutive mutations are represented by CPK spheres.