Extremophile
From Proteopedia
(Difference between revisions)
| (87 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
== Extraordinary Proteins == | == Extraordinary Proteins == | ||
| - | + | Life 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. In this article, we present the biophysical modifications present in extreme protein structures. | |
| - | + | ||
| - | == | + | == Positively charged myoglobin allows whales to hold their breath during long dives == |
| - | + | ||
| - | + | Elephants can hold their breath for 2 minutes, but whales can hold their breath for 60 minutes - and they do, migrating underwater around the world. To get a clue as to why whales can hold their breath for so long, several researchers gathered tissue samples from hundreds of aquatic and terrestrial mammalian species (mainly from museum collections)<ref name="whaleMyo"> DOI:10.1126/science.1234192</ref>. They measured the concentration of [[myoglobin]], the protein that stores oxygen in muscle tissue, which is used for muscle activity, and also sequenced each specie's myoglobin gene, and used this sequence - as well as the protein's mobility on a native gel (which depends soley on the 3D structure and charge - with myoglobin from different species all having the same overall 3D structure), when possible - to calculate the net charge of each myoglobin protein. | |
| - | : | + | |
| - | + | ||
| - | + | Amazingly, they found that aquatic mammals, across the mammalian phylogeny, independently had acquired the ability to hold their breath, by increasing the concentration of myoglobin, via increasing the net charge of myoglobin. Typically, purified terrestrial mammal's myoglobin has a solubility of 20 mg/g in an aqueous solution at neutral pH ([[http://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Product_Information_Sheet/2/m0630pis.pdf Sigma Aldrich]]) which turns out to be the maximum level of myoglobin found in most terrestrial mammal's tissue. But whales and other aquatic mammals far exceed this solubility limit, e.g., whales have 70 mg/g. The way that they overcome the solubility constraint may be traced back to a modest increase in the net charge of myoglobin - from around +2 in terrestrial animals to around +4 in aquatic animals. | |
| - | + | However, a 3-fold increase in concentration of myoglobin ought to result in a similar fold increase in max time of breath holding, and the researchers show that body mass also makes a critical contribution to an animal's ability to hold its breath, with the overall equation for the contribution of body mass and myoglobin net charge as follows: | |
| - | + | log (maximum time underwater) = 0.223*log(body mass) + 0.972*log(myoglobin net charge) + 0.891 | |
| - | + | As Asian elephant's weight is ~3K Kg, and a sperm whale's weight is ~50K Kg, it is clear that the modest increase in net charge contributes about the same as the enormous difference in body mass to the maximum time underwater. | |
| - | < | + | <StructureSection load='1mbn' size='350' side='right' caption='myoglobin (PDB entry [[1mbn]])' scene='55/557585/Align_test/5'> |
| - | + | ==Molecular Tour== | |
| - | + | The ability of increasing net charge to enable higher solubility is a known phenomenon<ref>doi: 10.1073/pnas.0402797101</ref>, and this study is consistent with previous reports<ref>PMID: 14741208 </ref>. The aquatic animals have increased their net charge in a variety of ways - different combinations of amino acids switches. We present one such manifestation of this overall trend, by comparing the elephant and whale myoglobin structures. | |
| - | + | ||
| - | + | It comes down to <scene name='55/557585/Align_test/18'>eight divergent amino acids (elephant's amino acids in yellow halos, and whale's amino acids without yellow halos, next to each other)</scene> that affect that charge - out of a total of 27 divergent amino acids. Without these eight differently charged 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 <scene name='52/523344/Elephantwhale/34'>surface residues</scene>. It is interesting to note that in this comparison (between whale and elephant) that there is no difference in net charge in the region in the vicinity of the heme group. This may reflect the key role of the heme group and residues near it, which can not be easily changed without a drastic affect on function. | |
| - | + | ||
| - | + | Calculate along the chain, 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) <scene name='52/523344/Elephantwhale/19'>residue position 8</scene> (<span style="color:red">'''glu'''</span> in elephents versus gln in whales), <scene name='52/523344/Elephantwhale/21'>12</scene> (<span style="color:blue">'''lys'''</span> vs. <span style="color:lightblue">'''his'''</span>), <scene name='52/523344/Elephantwhale/22'>27</scene> (thr vs. <span style="color:red">'''asp'''</span>), <scene name='52/523344/Elephantwhale/23'>34</scene> (thr vs. <span style="color:blue">'''lys'''</span> ), <scene name='52/523344/Elephantwhale/24'>87</scene> (gln vs. <span style="color:blue">'''lys'''</span> ), <scene name='52/523344/Elephantwhale/26'>116</scene> (gln vs. <span style="color:lightblue">'''his'''</span>), <scene name='52/523344/Elephantwhale/27'>132</scene> (<span style="color:blue">'''lys'''</span> vs. asn), <scene name='52/523344/Elephantwhale/28'>140</scene> (asn vs. <span style="color:blue">'''lys'''</span> ). | |
| - | + | '''note about this scene''': <span style="color:red">'''Asp and Glu'''</span> have a charge of ''-1'', <span style="color:blue">'''Arg and Lys'''</span> have a charge of ''+1'', <span style="color:lightblue">'''His'''</span> in the positions shown here - ''12'' and ''116'' (Table S2<ref name="whaleMyo" />) - have a charge of about ''+0.5''. | |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | < | + | |
| - | Some bacteria and even animals can survive great temperatures. Studying <scene name='JMS/sandbox5/Tbadh/1'>a thermophilic enzyme</scene>, Prof. Burstein noticed two special features that appear to explain this enzymes ability to maintain its structure in over 83℃! For comparison, you could fry an egg at 65℃, which mean all the protein in an egg denature at significantly less than 83℃. To demonstrate the special structural properties of the thermophilic enzyme underlies its thermophilic prowess, Prof Burstein selectively altered normal enzymes to have the two structural features, and indeed found that the normal enzymes had become thermophilic. The two properties relate to ∆H and to ∆S. Firstly, he found the thermophilic enzyme had a unique <scene name='JMS/sandbox5/Ion_network/4'>four amino acid binding-network</scene> that encompassed two monomers of the tetrameric enzyme, repeating between each monomer and its two partner monomers. This network apparently makes the oligomer more stable, or ∆H more negative. Secondly, the thermophilic enzyme was <scene name='JMS/sandbox5/Proline/2'>enriched for proline</scene>. Because proline's side chain has minimal degree of freedom, proline's, unlike other amino acids, are minimally restricted by folding. Therefore, ∆S is less negative. These two structural properties are labelled by the corresponding term in the thermodynamics equation:<br /> | ||
| - | ::<big><scene name='JMS/sandbox5/Tbadh/1'>∆G</scene> = <scene name='JMS/sandbox5/Ion_network/4'>∆H</scene> - T<scene name='JMS/sandbox5/Proline/2'>∆S</scene>.</big><br /> | ||
</StructureSection> | </StructureSection> | ||
| + | {{Reflist}} | ||
Current revision
Extraordinary Proteins
Life 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. In this article, we present the biophysical modifications present in extreme protein structures.
Positively charged myoglobin allows whales to hold their breath during long dives
Elephants can hold their breath for 2 minutes, but whales can hold their breath for 60 minutes - and they do, migrating underwater around the world. To get a clue as to why whales can hold their breath for so long, several researchers gathered tissue samples from hundreds of aquatic and terrestrial mammalian species (mainly from museum collections)[1]. They measured the concentration of myoglobin, the protein that stores oxygen in muscle tissue, which is used for muscle activity, and also sequenced each specie's myoglobin gene, and used this sequence - as well as the protein's mobility on a native gel (which depends soley on the 3D structure and charge - with myoglobin from different species all having the same overall 3D structure), when possible - to calculate the net charge of each myoglobin protein.
Amazingly, they found that aquatic mammals, across the mammalian phylogeny, independently had acquired the ability to hold their breath, by increasing the concentration of myoglobin, via increasing the net charge of myoglobin. Typically, purified terrestrial mammal's myoglobin has a solubility of 20 mg/g in an aqueous solution at neutral pH ([Sigma Aldrich]) which turns out to be the maximum level of myoglobin found in most terrestrial mammal's tissue. But whales and other aquatic mammals far exceed this solubility limit, e.g., whales have 70 mg/g. The way that they overcome the solubility constraint may be traced back to a modest increase in the net charge of myoglobin - from around +2 in terrestrial animals to around +4 in aquatic animals.
However, a 3-fold increase in concentration of myoglobin ought to result in a similar fold increase in max time of breath holding, and the researchers show that body mass also makes a critical contribution to an animal's ability to hold its breath, with the overall equation for the contribution of body mass and myoglobin net charge as follows:
log (maximum time underwater) = 0.223*log(body mass) + 0.972*log(myoglobin net charge) + 0.891
As Asian elephant's weight is ~3K Kg, and a sperm whale's weight is ~50K Kg, it is clear that the modest increase in net charge contributes about the same as the enormous difference in body mass to the maximum time underwater.
| |||||||||||
- ↑ 1.0 1.1 Mirceta S, Signore AV, Burns JM, Cossins AR, Campbell KL, Berenbrink M. Evolution of mammalian diving capacity traced by myoglobin net surface charge. Science. 2013 Jun 14;340(6138):1234192. doi: 10.1126/science.1234192. PMID:23766330 doi:http://dx.doi.org/10.1126/science.1234192
- ↑ Brocchieri L. Environmental signatures in proteome properties. Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8257-8. Epub 2004 May 24. PMID:15159533 doi:http://dx.doi.org/10.1073/pnas.0402797101
- ↑ Goh CS, Lan N, Douglas SM, Wu B, Echols N, Smith A, Milburn D, Montelione GT, Zhao H, Gerstein M. Mining the structural genomics pipeline: identification of protein properties that affect high-throughput experimental analysis. J Mol Biol. 2004 Feb 6;336(1):115-30. PMID:14741208 doi:http://dx.doi.org/10.1016/S0022283603014748
Proteopedia Page Contributors and Editors (what is this?)
Joseph M. Steinberger, Joel L. Sussman, Alexander Berchansky, Michal Harel
