Integral membrane proteins have functional asymmetry i.e. they have two different domains of proteins performing different functions. these proteins have Tyr and Trp amino acid residues at the interface between the lipid and water.Because these amino acids have dual nature that their side chains can interact with both extracellular aqueous environment as well as hydrophobic lipid phase and another generalization about amino acid location relative to bilayer is described by "positive inside rule": The positively charged Lys,His, and Arg residues of membrane proteins occur more commonly on the cytoplasmic phase of membranes.My question is that why only positively charged amino acids are faced towards cytoplasm why not negatively charged amino acids or other amino acids are favoured here?
Some thoughts on this. First of all, the positive-inside rule, proposed by Gunnar von Heijne, is an empirical rule based upon observations, not one derived from theoretical considerations, so any explanation is simply an attempt at a rationalisation.
Having said that, here are three of those rationalisations: