INDICATIONS OF A COMMON FOLDING PATTERN FOR VDAC CHANNELS FROM ALL SOURCES

Previous research on the mitochondrial channel VDAC from the yeast S. cerevisiae had identified protein strands forming the wall of VDAC's a queous pore. Here we report the results of analyzing the primary seque nces of VDAC from various sources to see if the transmembrane folding pattern identified from this yeast is conserved for VDAC of different species. We analyzed the primary sequences of VDAC from higher plants, fungi, invertebrates, and vertebrates and found that all have a very similar ''beta-pattern'' profile with 12-15 peaks indicating potential sided beta strands that are candidates for protein strands forming th e wall of the aqueous pore. All these VDAC sequences can be put into t he 13 transmembrane strand folding pattern previously identified for y east VDAC. These folding patterns agree with available experimental da ta: both electrophysiological and protease digestion data. Although th e primary sequences of VDAC from very diverse organisms show low homol ogy, sequence similarity in the proposed corresponding 13 transmembran e strands is substantial. Competing proposals utilizing 16 transmembra ne beta strands are in conflict with electrophysiological experimental observations and violate the constraints on such strands, such as no charged amino acids facing the phospholipid membrane and sufficient nu mber of residues to span the membrane.