Computation and mutagenesis suggest a right‐handed structure for the synaptobrevin transmembrane dimer

Biological membrane fusion involves a highly precise and ordered set of protein–protein interactions. Synaptobrevin is a key player in this process. Mutagenesis studies of its single transmembrane segment suggest that it dimerizes in a sequence specific manner. Using the computational methods developed for the successful structure prediction of the glycophorin A transmembrane dimer, we have calculated a structural model for the synaptobrevin dimer. Our computational search yields a well‐populated cluster of right‐handed structures consistent with the experimentally determined dimerization motif. The three‐dimensional structure contains an interface formed primarily by leucine and isoleucine side‐chain atoms and has no interhelical hydrogen bonds. The model is the first three‐dimensional picture of the synaptobrevin transmembrane dimer and provides a basis for further focused experimentation on its structure and association thermodynamics. Proteins 2001;45:313–317. © 2001 Wiley‐Liss, Inc.