Extremophile
Extraordinary ProteinsLife - DNA, Proteins, physiology, behavior, and all - has managed to weather extreme environments - almost every hole we've poked a stick into contains thriving living communities. Proteins are a necessity for living, and therefore tuning protein structures to an extreme environment is of paramount value to an evolving organism seeking an extraordinary niche. In this article we'll present the biophysical strategies apparent from some extreme protein structures. Positively charged myoglobin allows whales to hold their breath during long divesWhales and elephants are both large animals that take life slow - walking slow, singing slow. But whales swim underwater while holding their breaths for long periods of time, and elephants can not: Why can whales hold their breaths for long, and elephants can not? One clue to this discrepancy is the difference in concentrations of myoglobin in whale and elephant muscle tissue: More myoglobin means more oxygen storage capacity, and whales have over 15 times the concentration of myoglobin as elephants do (70 mg/g wet mass compared to the elephants 4.6). But this leads to a biophysical question. A very high concentration of myoglobin should lead to aggregation, which would prevent myoglobin from functioning, so how do whales' myoglobin deal with this extreme demand, and why can't elephants' myoglobin accumulate to high concentrations as well? In a recent article in Science[1], the laboratories of Professors Berenbrink, Campbell, and Cossins demonstrate that natural variation in net positive charge explains aquatic and terrestrial animals' different diving abilities. Following this pattern, whale myoglobin has a net charge two formal charges higher than in elephants: +4 compared to +2 in the elephant. Apparently a protein's solubility is a function of its net charge[2], where a protein with a higher net charge is much more soluble. It comes down to eight divergent amino acids (elephant's amino acids in yellow halos). Without these amino acids, myoglobin in both whale and elephants has a charge of +1. With them, whale myoglobin has a net charge of +4 and elephants of +2. Importantly, all eight of these divergent amino acids are surface residues. Calculate along the chain, in the N to C-terminal direction how just several amino acid switches bring the positive net charge of whale myoglobin up to +4 and elephants to +2: (summing up the total charge of the protein) residue position 8 (glu in elephents versus gln in whales), 12 (lys vs. his), 27 (thr vs. asp), 34 (thr vs. lys ), 87 (gln vs. lys ), 116 (gln vs. his), 132 (lys vs. asn), 140 (asn vs. lys ).
Considering that the proteins in the Protein Data Bank have net charges that tend to fall between -10 and +10[3] , it may seem surprising that an increase of just +2 results in such a huge increase in solubility. Consider though that many life processes, protein folding is a great example, exist in a near equilibrium state, where a relatively tiny change in enthalpy or entropy can push the system to one direction or the other. In the case of solubility, where often the first dimer is neccessary to begin aggregation, a small bias away from forming dimers may be sufficient to prevent nucleation of aggragation, and hence increases the molecule's solubility.
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Joseph M. Steinberger, Joel L. Sussman, Michal Harel, Alexander Berchansky
