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<StructureSection load='' size='500' side='right' caption='myoglobin (PDB entry [[1mbn]])'  scene='57/575026/Electrostatics/10'>
<StructureSection load='' size='300' side='right' caption='cryptochrome (PDB entry [[1u3d]])'  scene='58/585079/1u3d_simple/1'>
<!-- <StructureSection load='1mbn' size='350' side='right' caption='myoglobin (PDB entry [[1mbn]])' scene='57/575026/Electrostatics/10'> -->
[[Image:1u3d.png|250px|left]]&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
[[Image:1a6m.png|250px|left]]&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
'''Extraordinary Proteins.  Extreme''' lifestyles sometimes require sensing the earth's magnetic field. Trytophan and aspartic acid residues may be key to an organism's ability to pick up where it is relative to Earth's magnetic poles.
'''Extraordinary Proteins.  Extreme''' lifestyles sometimes require increasing the abundance of a protein with critical properties. We present the role charged amino acids - such as aspartic acid, glutamic acid, arginine, histidine and lysine - can have in changing a protein's solubility.


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'''Elephants''' can hold their breath for 2 minutes, but whales can hold their breath for 90 minutes - and they do, migrating underwater around the world. To find out how, a group of researchers contacted museums and zoos around the world<ref name="whaleMyo"> DOI:10.1126/science.1234192</ref>.
'''Birds, turtles, butterflies and other animals migrate''' with the help of the compasses built into their bodies. Drs. Schulten and Solov'yov described a mechanism taking place within the birds' retina tissue, inside the rod cells, inside cryptochrome proteins known to process blue light for entraining circadian cycles, but now perhaps also deserving to be known as the seat of these organism's ability to sense magnetic fields<ref>doi:10.1529/biophysj.106.097139</ref>.  
 
'''They hypothesized that a vital element of whales''' and other aquatic animals' ability to hold their breath for so long is storage of more oxygen in their muscles by increasing the concentration of '''[[Myoglobin]]''', the protein that stores oxygen in muscle tissue.
 
Specifically, they predicted that species could increase the concentration of myoglobin by increasing its solubility through increasing the number of positively charged regions on the protein's surface, so that even at high concentration the electrostatic repulsion between the myoglobin proteins would prevent their aggregation.
 
'''Amazingly, they found an association''' between an animals' ability to hold its breath, higher concentrations of myoglobin in muscle tissue, and an increase in its net charge (taken as a ''proxy'' for an increase in the number of positively charged regions on the surface). 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.


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'''Molecular Tour:'''
'''Molecular Tour:'''


The ability of an increase in number of positively charged regions 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 number of positively charged regions through key substitutions of neutral amino acids for positively charged amino acids, and of negative amino acids for neutral or positive amino acids. We present one such manifestation of this overall trend, by comparing the elephant and whale myoglobin structures.
The <scene name='58/585079/1u3d_magnet/19'>cryptochrome protein</scene> absorbs a single photon of blue light of 2.7 eV, exciting either of the FAD ligand's two nitrogen atoms, which are involved in resonance (and shown in halos, as are the <scene name='58/585079/1u3d_magnet/24'>all the relevant atoms</scene>). This FAD nitrogen atom is protonated by a nearby aspartic amino acid (the proximate donors shown with halos), and the electron hole is filled through a series of electron transfers from the three tryptophan amino acids (the nitrogen donors shown with halos). Notably, as seen in this alternative view, FAD and the three tryptophans  <scene name='58/585079/1u3d_magnet/21'>form a chain</scene> from the protein's inside to its outside. At this stage, where FAD is in its active signaling state, the extra electron on FAD and lone electron on the final tryptophan amino acid (324) <scene name='58/585079/1u3d_magnet/25'>have formed a radical pair</scene> (location of the electrons shown with halos). The pair is entangled, but only when they spin in the opposite directions, can the extra electron on FAD return and fill the hole left in tryptophan 324.
 
Out of 27 divergent amino acids between whale and elephant's myoglobin - from a total of 153 amino acids - only 8 of these amino acids lead to changes of charge. These eight amino acids are shown for whales and elephants, <scene name='57/575026/Electrostatics/22'>side by side</scene>. Arginine and Lysine have a charge of +1, aspartic and glutamic acids have charges of -1, and histidine in positions 12 and 116 have a charge of about +0.5 (supplementary Table S2 <ref name="whaleMyo" />). The whale amino acids, have an illustrative eletrostatic field drawn around the <scene name='57/575026/Electrostatics/23'>electrically charged atom</scene> in the residue. Note that the effective size of the electric field of the charged atom at the end of residues like lysine is actually larger, because of the multiple conformations a long residue like lysine moves between. Next to the whale amino acid, the <scene name='57/575026/Electrostatics/18'>elephant residues</scene> are shown in yellow halos and labelled with the residue name. From studying the differences between these two proteins, it is clear that the whale protein has more areas with a positive electrostatic field. These positive electrostatic fields are <scene name='57/575026/Electrostatics/19'>scattered about the surface</scene> of the whale protein, and will repel any whale myoglobin, preventing the protein-protein interactions that lead to aggregation.  
Researchers Klaus Schulten at University Illinois at Urbana Champaign and Ilya Solov'yov, now at the University of Southern Denmark, connect this system to the fascinating ability of many birds, and other flying species, to migrate while sensing the earth's magnetic field. Through simulations, they show that where the bird's cryptochrome compass's <scene name='58/585079/1u3d_magnet/23'>"FAD-trp324 needle"</scene> (shown as a dotted line) is aligned with the line  extending between the earth's poles, the entangled electrons will 'on average' spend more time spinning in the same direction, and therefore by delaying the electrons return to trp324, FAD will 'on average' be in its signalling mode for longer.  


Another way to say this, in the case of proteins <scene name='57/575026/Electrostatics/16'>in solvents such as water</scene>, is that, for each and every protein, <scene name='57/575026/Electrostatics/24'>water binds to the hydrogens</scene> (e.g., lysine's ammonium at physiology pH has three hydrogens - not shown) coming off a positively charged atom, or associates with the charged atom itself, thus screening each protein from the other proteins.  
Therefore, as a possible explanation, because many cryptochrome proteins are involved in registering blue light photons - millions of proteins per cell, and many cells across the retina, a change in the average time spent in the signalling state - "the transition rate" - is perhaps measured by the brain as the time until 50% of the cells do not have active FAD molecules. By moving its head about in different directions, a bird can find position at which the signalling last longest. That places the bird along the world's north-south pole axis.  


Still, this picture is incomplete. While illustrative of the basic principles of how small electrostatic fields changes can greatly increase a protein's solubility, there other contributing factors to the electrostatic field, e.g.,  solvated ions, crowding conditions, and the neighboring residues to these divergent residues. For example, when a negatively charged residue neigbors one of these additional positive residues, then from a distance relatively larger than the distance between the two oppositely charged residues, the electrostatic field is zero.
<!--
this is similar to what is known for <scene name='58/585079/Diamond/3'>nitrogen vacancy centers</scene>.
showing the <scene name='58/585079/Diamond/4'>molecular symmetry</scene>.
-->


<!--
<!--
'''Modest increase in net charge contributes about the same as the enormous difference in body mass to the maximum time underwater.   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:
<scene name='58/585079/1u3d_magnet/30'>cornell</scene>
also see march 2017 molecule of the month by david goodsell.


''log (maximum time underwater) = 0.223*log(body mass) + 0.972*log(myoglobin net charge) + 0.891''
Mechanistically, the propensity of the electrons to spin in one direction or the other is affected by a local magnetic field, which is in this case primarily determined by the nuclear spins of several <scene name='58/585079/1u3d_magnet/22'>key nitrogen and hydrogen atoms</scene> (naming, as in fig. 5 of Schulten et al., 2007), the current spin state of the entangled electrons, '''and the external magnetic field (emanating from earth)'''. Only when the line between FAD and trp324 is parallel to the line connecting the north and south poles, is the earth's (external) magnetic field biasing the electrons spins to the same direction (parallel;triplet) spinning. Otherwise, the nuclear spins are the main determinants, and the the spins are approximately equivalently likely to be in the same or opposite directions.  
-->


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.
<!--
(But how a bird know whether it is facing due north or south is a question which cannot be figured out using this protein compass, the research emphasize in their study).
<scene name='58/585079/1u3d_magnet/26'>showing asp390 (or 387 in cry2) that is critical for photoreception - no homo or heteroassociation</scene>
<scene name='58/585079/1u3d_magnet/27'>showing the substitution of tucker which results in cry2oligo</scene>
<scene name='58/585079/1u3d_magnet/28'>BLUE 374 weak as full, weaker, but still constitute as phr. DARK 387 is never bound.</scene>
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</StructureSection>
</StructureSection>


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=References:=
=References:=
{{Reflist}}
{{Reflist}}
* [http://www.ks.uiuc.edu/Research/cryptochrome/ Cryptochrome and Magnetic Sensing], ''Theoretical and Computational Biophysics Group'' at the University of Illinois at Urbana-Champaign

Latest revision as of 23:31, 16 June 2019

     

Extraordinary Proteins. Extreme lifestyles sometimes require sensing the earth's magnetic field. Trytophan and aspartic acid residues may be key to an organism's ability to pick up where it is relative to Earth's magnetic poles.

Birds, turtles, butterflies and other animals migrate with the help of the compasses built into their bodies. Drs. Schulten and Solov'yov described a mechanism taking place within the birds' retina tissue, inside the rod cells, inside cryptochrome proteins known to process blue light for entraining circadian cycles, but now perhaps also deserving to be known as the seat of these organism's ability to sense magnetic fields[1].

Molecular Tour:

The absorbs a single photon of blue light of 2.7 eV, exciting either of the FAD ligand's two nitrogen atoms, which are involved in resonance (and shown in halos, as are the ). This FAD nitrogen atom is protonated by a nearby aspartic amino acid (the proximate donors shown with halos), and the electron hole is filled through a series of electron transfers from the three tryptophan amino acids (the nitrogen donors shown with halos). Notably, as seen in this alternative view, FAD and the three tryptophans from the protein's inside to its outside. At this stage, where FAD is in its active signaling state, the extra electron on FAD and lone electron on the final tryptophan amino acid (324) (location of the electrons shown with halos). The pair is entangled, but only when they spin in the opposite directions, can the extra electron on FAD return and fill the hole left in tryptophan 324.

Researchers Klaus Schulten at University Illinois at Urbana Champaign and Ilya Solov'yov, now at the University of Southern Denmark, connect this system to the fascinating ability of many birds, and other flying species, to migrate while sensing the earth's magnetic field. Through simulations, they show that where the bird's cryptochrome compass's (shown as a dotted line) is aligned with the line extending between the earth's poles, the entangled electrons will 'on average' spend more time spinning in the same direction, and therefore by delaying the electrons return to trp324, FAD will 'on average' be in its signalling mode for longer.

Therefore, as a possible explanation, because many cryptochrome proteins are involved in registering blue light photons - millions of proteins per cell, and many cells across the retina, a change in the average time spent in the signalling state - "the transition rate" - is perhaps measured by the brain as the time until 50% of the cells do not have active FAD molecules. By moving its head about in different directions, a bird can find position at which the signalling last longest. That places the bird along the world's north-south pole axis.



cryptochrome (PDB entry 1u3d)

Drag the structure with the mouse to rotate


References:References:

  1. ↑ Solov'yov IA, Chandler DE, Schulten K. Magnetic field effects in Arabidopsis thaliana cryptochrome-1. Biophys J. 2007 Apr 15;92(8):2711-26. Epub 2007 Jan 26. PMID:17259272 doi:http://dx.doi.org/10.1529/biophysj.106.097139

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