Earlier we talked about how atoms - like those making up all of these different charms we’re discussing, link together through strong covalent bonds where they share pairs of electrons. The electrons in a covalent bond can be shared “fairly” or “unfairly” - fair sharing occurs when the partners have similar electronegativities (electron-hoginness), such as carbon and hydrogen, and it leads to an even charge distribution (non-polar). “Unfair” sharing happens when one of the sharers is more electron-hogging (electronegative) than the other - it’ll pull more of the shared electrons toward itself, leading to a partial charge imbalance we call polarity. You often see such “polar covalent bonds” between oxygen or nitrogen (which are both highly electronegative) and carbon or hydrogen - the O or N steals more than its fair share, leading it to be partly negative and leaving its bonding partner partly positive. Opposite charges attract - even partial ones - so the partly positive parts of polar molecules like to hang out with the partly negative parts of other polar molecules (or other fully charged things). Water is highly polar, so water molecules really like to hang out together. Thus, if you want water to hang out with something other than water you want that thing to be more attractive to a water molecule than another water molecule. If the water likes it (which happens if the thing is highly polar or charged), it’ll “dissolve” (get a full water coat) - we call such water-loving/water-loved things hydrophilic. Otherwise, the water will just “exclude” the thing from its network, leaving the excluded things to group together to make their surface area as small and hidden as possible. We call this the “hydrophobic effect” and it’s the main force behind protein folding - nonpolar amino acid residues are “hydrophobic” because they don’t have even partial charges to offer - so they fold up so that they’re in the protein’s interior, or at least facing away from the water.more on the hydrophobic effect here: bit.ly/hydrophobiceffectPSA The extreme of this is seen with fully-charged amino acids. There are 2 side chains that are frequently negatively-charged at physiological (normal bodily) pH, Aspartic acid (Asp, D)(pKa ~3.65) & Glutamic acid (Glu, E)(pKa ~4.25). We call these acidic because they donate H⁺s & when they do they become negatively charged & now capable of accepting H⁺s (acting as a base) so we call them “conjugate bases.” It can seem kinda confusing because “acidic” residues often play important roles by acting as bases in their deprotonated form. The “acidic” refers to its neutral form being acidic. There are 3 side chains that are frequently positively-charged & protonated at physiological pH - we call these “basic.” Lysine (Lys, K) (pKa ~ 10.28) & Arginine (Arg, R) (pKa ~13.2) are predominantly protonated at cellular pH, but Histidine (His, H) (5.97) is more “iffy” (that pKa tells you when HALF the groups are deprotonated on average so it’s not like you hit the pKa & bam they’re all deprotonated - you have a mix. Also, an important caveat is that pKas are context-dependent so the pKa you get from a table is likely close to but not exactly the “real” pKa in the situation you’re looking at). much more on protein charge here: bit.ly/ionexchangechromatography Protein structure can also be affected by post-translational modifications - things added onto the protein after the amino acid is put into the chain - such as phosphorylation (addition of phosphate groups which are bulky negatively-charged things) or glycosylation (addition of sugar chains). These alterations can make the protein have to rearrange to make everyone comfy again. Protein folding doesn’t always go right and sometimes it needs help. If a protein misfolds, machinery in the cell can try to refold it and if that fails, the proteasome can shred it up so aggregated (clumped-up) proteins don’t build up & become toxic to your cells (this is often a problem in some neurodegenerative diseases). But proteins can also get help during the translation process to make proper folding more likely. Basically, during translation, the amino acids are linked (w/help of ribosomes) 1 at a time to the end of a growing chain, going from N terminus to C-terminus. The protein chain starts folding as it emerges from the ribosome’s “chimney,” sometimes with the help of proteins called chaperones which can help hide hydrophobic parts that are coming out before the part of the protein that they’re ultimately going to “hide with” comes out. I talk more about this sort of thing here in my post on when you’re trying to get cells to make a protein for you (recombinant expression) and it’s not going well… : bit.ly/wherestheprotein more about all sorts of things: #365DaysOfScience All (with topics listed) 👉 bit.ly/2OllAB0 or search blog: thebumblingbiochemist.com
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