Myoglobin is a small (153 amino acids) protein belonging to the globin family of proteins. Themain function of globin proteins involves the transport, facilitate, or in the case of myoglobin, storeoxygen via binding of the iron complex heme domain of the globin protein. Myoglobin specificallycontains eight alpha helices connected by loops and one heme domain, all of which remains moderatelyto highly conserved, which highlights the importance and high level of function the protein plays inoxygen interactions. While important in all walks of life, myoglobin concentrations are significantlyhigher in diving mammals than terrestrial mammals. This stems from the nature of diving and requiringoxygen to be stored in muscles to provide mammals with extended diving stints, showing a potentialevolutionary trend toward fulfilling a diving niche.
Myoglobin was the first protein to be characterized by x ray crystallography, and since then ithas been widely characterized. Most important are studies that confer potential adaptation for myoglobincontaining organisms, and most importantly, diving species. Due to these studies it is now widelyaccepted that higher concentrations of myoglobin are directly correlated with length of dives (1) (2).These studies at the time did not account for differences in mass. However more recent studies haveshown that mostly (with several outliers) mass and myoglobin concentrations were directly correlated,and further correlated with time of dives (3).
Unfortunately these studies failed to differentiate betweenheavily muscular versus fattier groups, since myoglobin is predominantly found in muscle and morespecifically the greatest force producing muscles (1). Most interestingly to us however are recent studiesthat examined the net charge of the myoglobin structure as it pertains to myoglobin aggregations, andfurther phylogenetically traced surface charge and correlated myoglobin concentrations and estimateddive times (2). These surface charges since have been recognized when identifying the heme oxygenbinding affinity but lack direct connection between charge and binding affinity.While the gaps in knowledge for myoglobin modeling are neither large nor glaring, there aresmall holes that we want fill in order to move towards a more complete myoglobin model. Our interestsas it pertains to our study are three fold. Our first two interests stem from myoglobin surface charge andits affect on concentration and oxygen affinity, and the third seeks to further research relating to massand concentration.The first two experiments we wish to run go hand in hand as they both pertain to myoglobinsurface charge. Firstly, we wish to look at what, if any, the optimal net surface charge for myoglobin isas it relates to functional concentration.
Previous research has postulated that myoglobin surface chargedeveloped as a way to circumvent having a higher concentration without allowing aggregation, whichinhibits oxygen binding (2). These studies traced charge phylogenetically to show that newer, longerdiving species have a higher absolute charge correlating to higher myoglobin concentration whichexplained the longer dives. The study however did not examine the relationship between charge andconcentration on a more precise level. The study did not account for the possible effect of surface chargeon oxygen binding affinity either.We wish to examine these gaps by running computational studies using modeling software suchas SWISS-MODEL or programmable math software such as mathematica. The first study will simulatemyoglobin packing within a given volume, using parameters for electrostatic forces defined bycoulombs laws and for newtonian spring potential forces and harmonic occillators, with the principlevariable being changing absolute charge assuming all myoglobin proteins contain the same charge perstudy.
The second study will utilize the same principles,with slightly different parameters to account for ironoxygenbinding.These study will yield information that will reporton the nature of surface charge and its potential effect onother physical properties. The results should also shedlight on expected post translational modifications orsingle nucleotide polymorphisms based on charged anduncharged amino acids as a way of regulating charge andthus function.
We expect to see a normal distribution (seeFigure 1) of functional myoglobin concentration versuscharge, resulting in a peak concentration with acorrelating optimal charge. This result is supported byprevious research as well as by the laws of physics (2).Low charge leads to high concentration of myoglobinwhich would aggregate and inhibit binding, which results in low functional myoglobin concentration.Higher charges leads to excessive repulsive forces that result in widespread myoglobin spreading whichis very inefficient, thus a lower concentration.From the oxygen binding computational study we expect to see little to no effect of charge onbinding. This is because the heme constituent is deeper within the cluster of the eight alpha helices, andthe surface charge would be too far to have a significant effect. There could be a slight effect in eitherdirection on charge changes resulting from amino acids near or in the heme binding constituent,however these amino acids are highly conserved and are very unlikely to change.While these computations are being run there will be more hands on work being done.
One studyhas correlated mass with dive time (3). Since myoglobin is found in primarily muscle, we would like tolook at species with varying muscle/fat compositions of equal weight. Specifically we would like to lookat sperm whale Physeter macrocephalous, Cuvier’s beaked whale Ziphius cavirostris, and Blainville’sbeaked whale Mesoplodon densirostris. Ideally we would like to look at as many species as possible buttime and travel will be working against us, so working in groups or even only observing. a single specieswill do.
These species were chosen based on their long dive times, and the latter two for diverging fromthe mass to dive time ratio (3). The ideal experiment would involve gathering a group of one specieswith relatively equal (within 5% of each other) mass and varying muscle/fat ratios, and observing themyoglobin concentrations from major muscle groups, as well as dive times if possible.We anticipate to see higher myoglobin concentrations and longer time of dives in the moremuscular groups. This would make sense as myoglobin is primarily found in muscle. These results,along with the results of the two computational studies not only fill in gaps on myoglobin modeling butprovide a foundation for possible adaptational predictions based on niche fulfillment.
As oceans start towarm due to global warming the niche for longer diving mammals becomes even more important, andwe may see a trend towards more muscular mammals as the need for insulating fat decreases. Longerdives allows mammals to hunt longer for food, as well as dive deeper to darker parts of the ocean thatsunlight cannot reach allowing protection from heat and ultraviolet sun rays.References:(