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.
Fleming
K G
KG
Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA. karen.fleming@jhu.edu
Engelman
D M
DM
D000465:Algorithms; D000818:Animals; D019281:Dimerization; D006021:Glycophorins / Q000737:chemistry; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D016296:Mutagenesis; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D050683:R-SNARE Proteins
D006021:Glycophorins; D008565:Membrane Proteins; D050683:R-SNARE Proteins