this video was brought to you by my supporters on patreon learn how you can make more episodes of this show by visiting patreon.com clockworkshow what you're looking at right now is one of the most ancient and fundamental machines common to almost all life on earth and looking at it work and really does look like a machine right this is a motor it's called atp synthase it is integral for both the beginning and end of every food chain on earth atp synface is one of the most important and beautiful structures in the universe and if you give me a few minutes i'll tell you how it powers you through everything you do even sitting here watching this video on youtube [Music] and here's the cool thing about atp synthase right this video is both part three of my series on photosynthesis and part four of my series on cellular respiration hit that subscribe button and you'll learn how atp synthase helps store solar energy in plants and then convert that very same energy from the food you eat no matter what the story is the same we're taking raw energy and converting it into something cells can actually use in plant cell chloroplasts the atp here will be used to convert carbon dioxide into sugar well glucose really thereby storing the energy plants captured from sunlight in your mitochondria and in plant mitochondria too actually atp synthase makes atp using the energy from those very same sugars regardless this happens because it's atp synthase's job too you guessed it synthesize atp this is adenosine triphosphate in your body and in every living thing ever it's the currency used to move energy around a cell need to get something done pay with little atp you can't just like plug your body into a battery or something it takes a lot of energy to be alive and that energy has to be mobile throughout your cells ready to be called upon in an instant atp does this by freely floating around in the cytoplasm of every one of your cells until some process needs energy and then atp pops off one of its phosphate groups releasing that energy and catalyzing whatever your cells need to do multiply that a few quadrillion times and that's basically a few minutes of your life nice but i'm getting ahead of myself we uh we gotta make the atp first and then we can use it so how on earth are we going to pull this off so regardless of whatever playlist you're on the setup here is essentially the same on one hand we're at the end of the light dependent reactions of photosynthesis we've harnessed sunlight and used that energy to cram as many protons as possible into the thylakoid inside our chloroplast on the other hand our mitochondria have metabolized food and used that energy to cram as many protons as possible into the intra mitochondrial membrane either way no matter what context you're thinking about this we've got a membrane with a huge concentration gradient to deal with these protons are willing to do pretty much anything to get across this membrane because they're so crammed together and the only way they're going to do it is through atp synthase that's awesome but even though on both counts i've been talking about this for basically almost an hour i feel like i need to do a real quick tangent right here like what are the protons even doing in this cell in the first place without being completely steeped in chemistry twitter all day me just casually throwing words around like this might be a little bit much and our understanding of how atp synthase and really all life at the chemical level does what it does we'll come down to this as humans we're kind to set up for failure when studying chemistry because the chemical we're made the most of and the chemical we interact the most with on a daily basis is so completely weird i'm talking about water water is bonkers compared to other chemicals unlike basically any other substance its solid form floats on top of its liquid form it forms goofy little beads like this and has surface tension among so many other just odd things those two genuinely weird properties are like that for the same reason i can go really in depth here i can literally talk about this all day but the weirdness of water that we care about today boils down to the fact that every single water molecule is kind of like a magnet no seriously like any magnet these water molecules have a positive and negative end it's not a super strong charge or anything but in aggregate it adds up this means that opposite charges will attract each other and like charges will repel each other so like why does this matter while that charge is so powerful that sometimes water can just straight up dissolve itself h2o can break down into just h which is a naked hydrogen nucleus and o h the hydrogen nucleus is literally just a single proton that's why you see them getting drawn as h plus without a negative electron to balance things out this is just a positive proton hanging out in your water so that's how protons get into your water sometimes there's more sometimes there's less and in previous videos you've seen how plants try to take advantage of this by cramming as many protons as possible inside the thylakoid inter-mitochondrial membrane and now that we've established this concentration gradient we can finally get to the actual meat of the video what am i like six minutes into this thing and we haven't even talked about atp synthase yet awesome why do you think biology class is like 80 memorization you need a lot of context to appreciate how this works i promise your patience is going to be rewarded here though so we've got our proton gradient nice how is atp synthase designed to take advantage of that atp synthase is largely broken into two major complexes you've got the f-zero complex down here buried deep in the membrane that's going to be our actual motor and up here is the f1 complex that's what gets powered by the motor like your car has an engine and it turns a wheel and watching this animation i hope you get the sense that i'm not being metaphorical here in the exact same way that a rotating turbine generates electricity in a dam or power plant or a water wheel gets turned by water to like do a thing the flow of protons inside your cells turns a motor which generates the energy you need to be alive that motor being this f-zero ring that i've been talking about so much let's dive deep into this wheel f0 and understand what we're dealing with here i'm going to zoom in here and give us a more detailed look into how proton flow turns f0 like a motor all right down here there's a channel for protons to flow in and interact with f0 f0 is just a ring of your classic alpha helices arranged in a circle like this you've got 12 helices on the outside which is where the protons will get stuck one helix at a time it's kind of hard in 2d to see how this is a wheel so let's flip to a view from the top real quick as you can see i wasn't kidding our helices are for real arranged in a ring and each helix picks up one proton at a time remember these protons are desperate to get in here because of how packed together they are on the other side of this membrane but in order to get where they want to go the only way is through this ring bound to one of these helices these protons will rotate all the way around counterclockwise and then pop off almost in the exact same place they started if we flip back to a side view you get a better sense of the overall proton direction they pop up through this dark green half channel attached to a helix and then take a ride all the way around the back half of f zero until they come all the way back around and pop off a little to the left of their starting point moving up through another dark green half channel down is where there's a lot of protons up is where there are not a lot of protons and protons want to get as far away from each other as possible which is what's powering this whole thing and honestly that's where most biology textbooks stop it's where i could stop too i could just say that the flow of protons is what spins f0 and that would honestly be good enough but i didn't just spend several minutes going on about water and magnets and charges and whatever just for it to be meaningless there's more to this story if you want to dive into the chemistry a little bit deeper ready let's go the part of these helices that actually matters is almost right in the center it's these two red circles this is me abstracting out an amino acid called aspartate you might see this one get called aspartic acid in your textbooks or whatever but right now we're called to get aspartate just like water aspartate has a charge that we can work with and right now in this particular helix our aspartate is developing kind of a negative charge which means it's just giddy to accept a proton here to ride around the f-zero ring now this is where it gets weird if you logic this out you'd think that the protons are positive so the next proton coming in pushes the other one out of the way and turns the ring that logic bears out right but this is where it gets weird because it isn't protons entering the ring that drives the motor it's not pushing the motor it's protons leaving that drives this motor remember structure equals function and protein structure is very very malleable so it's not just the ring that's important it's what's anchoring the ring to the membrane as well it's hard to show you in 2d but i'm showing you a little piece of the a subunit that's helping hold f0 inside the membrane without spinning out of control this blue subunit right here is holding on to an argonine amino acid unlike aspartate this argonine has a decent positive charge so when our aspartate holding a proton makes it to this part of the turn things get pretty wild that positive charge pushes on our proton just enough that aspartate deprotonates the proton just pops off there's a second channel up here that's designed to attract protons a little bit so it's going to go that way and losing that proton changes everything for aspartate remember aspartate in this situation kind of has a negative charge and argonine has enough of a positive charge to push our proton away so now aspartate feels pulled towards argonine and that pull is enough to bend this whole helix violently this vending is so powerful that it turns the whole ring so it's this charge right here that's doing a lot of the work in terms of making this motor turn so instead of being pushed by protons our ring is being pulled by a difference in charge it doesn't last for long though since our helix will get pulled just enough to be right over the bottom half channel once again ready to go back to normal once a new proton swoops in and attaches to aspartate but this happens again and again and again and again all the way around the ring as long as there's protons powering it so i'm summing this up and really driving it home here f-zero turns because of the proton flow it's just like a water wheel if somehow the water caused the wheel to pull itself forward instead of just pushing on it at the end of the day all that matters is that f-zero was spinning pat yourself on the back for making it this far through like the really dense chemistry you nailed it it's all gravy from here on out let's find out what we're gonna do with the power this motor is generating we got a spin going but what is spinning so in the middle of our f-zero unit is the start of the f1 complex the second half of atp synthase this stock is the axle that our motor drives taking away the business end of the f1 complex you can see the stock is kind of curved as the curve of this axle turns it engages with the top part of atp synthase this little egg dome looking bit is actually made up of six subunits a hexamer you have three alpha and three beta subunits up here the alphas are just here to hold everything together and the betas are going to be where the magic actually happens remember we've gone through a lot a lot of a video just to get to the moment where we synthesize atp this is where that happens and it works by taking everything we've learned so far from this video and applying it one more time these beta subunits have three different shapes depending on where the stalk is pointing and we can use those three shapes to build our little atp molecule i'm gonna flip back out to our view from the top because it's just a little easier you've got the stalk in the middle rotating counterclockwise now this is the part of the video where i shave a bunch of details off so we don't end up stuck here for an hour there are so many tiny fascinating little interactions here that help change the shape of these beta subunits but i'm going to stick to the most important stuff i.e the fact that the shape changes just so we can stick the landing and get you back to your life i'm gonna pause this here and all i want you to do is watch the pointy bit of our axle here try to follow it all the way around without getting distracted by all the motion in the rest of this animation this pointy bit is the important end of our axle notice how as the point engages with these betas those beta subunits open up wide that is the first stage of atp synthesis our little beta press opens up and is ready to accept two things a molecule of adp and a free phosphate ion an inorganic phosphate if you want to get technical about it adp is adenosine diphosphate i.e just two of them atp gets its superpowers from having a third phosphate group crammed onto the end here we'll get to that just watch a few full rotations since there's three copies here our beta subunits have three different shapes they cycle through open loose and tight by cycling through these beta here becomes a kind of press like literally a printing press shoving a phosphate ion onto adp forcing it to become atp it's so similar to an assembly factory line that it kind of blows my mind every time i review this but let's watch how this happens i'm going to flip to a side view to make this a little bit more clear and we're going to zoom way in so i'm flipping this to a side view of just one beta press we're in the open confirmation right now like the name suggests this confirmation is the most open and able to accept a new adp and a phosphate this works just like a puzzle but with magnets so an adp floats on in here and the shape of the beta press is perfect so that the charges in the adp molecule line up with opposite charges in the press so it slots in here and sticks by way of hydrogen bonds a free phosphate ion floats in and does the same thing in this spot just a little bit more over here then the stalk rotates enough to engage the loose position this helps get the adp and phosphate cozy together and one thing that's hard to show in 2d is that the phosphate gets warped a little bit to make bonding a little easier and then a little more rotation gets us to the tight position where adp and phosphate are shoved together so tightly they bond together and become atp and then we go back to the open position where atp is now free to leave and then a new adp comes in and the cycle continues from there the best metaphor is that this is an atp printing press all of that detail all of that setup comes into literally just shoving these two bits together until they bind but more importantly that is the end of the journey you've got all the details now to see how rotational energy turns adp into atp and now that atp is going to go off and just do cellular business of all the things i animate in biochemistry this is the one that's the most mechanical the precision the form and function here are so machine like it always puts a kind of quiet in me when i think about how this machine has existed for billions of years only for people powered by this very machine to come along and make like dams and nuclear power plants and steam engines that harness and distribute energy with like the exact same principle or an incredibly similar principle what's even more incredible is when you think about atp synthase from the perspective of the food chain like i said this is part three of my photosynthesis series the atp synthesized here in the chloroplast will go on to help store energy by turning carbon dioxide into sugars those sugars go on to be eaten by herbivores and maybe even by you with a few other herbivorous and or carnivorous intermediates either way that food is metabolized and that energy is used to power the same machine not because you're powered by atp synthase but because atp is this brilliant way of storing and moving energy around a cell energy isn't super useful to life unless it can be stored and called upon what's beautiful about atp synthase is that it forms a circle between the beginning and the end of the food chain atp synthase is what turns sunlight into something plants can actually store as food and when those plants get eaten or the things that ate those plants get eaten by you atp synthase is what you use to finally unlock that stored sunlight in that food turning that energy into something your body can actually use to maintain the delicate dance of you being alive make no mistake you are solar powered there's just a couple of intermediate steps in between so atp synthase is just there a cool little middle finger raised up to entropy and chemical equilibrium trending out everything you need to keep functioning trillions upon trillions of times every second and here you are using all that energy to sit there watching a video on youtube nice you know actually that's a terrible joke because it's exactly the opposite of the point i want to make because you took the time to power through 15-ish minutes of understanding the goofy and fiddly fundamentals that serve as your molecular foundation and you can feel bad that you're using the incredible power of these motors just to hang out on youtube or you can look at it in a different way you can see the delicate power here and know that this is just an infinitesimal slice of the balancing act that just allows you to be alive i look at atp synthase and all the wondrous chemistry that it powers and i see a more fundamental truth i see just how much work it takes to keep you alive the incredible amount of chemistry that just lets you sit there and feel something anything and it makes me believe to my core that this machinery alone makes you deserving of dignity no matter how bored or low you might feel about yourself i know there is an entire inner cosmos burning away allowing that to happen no matter how mundane or boring you might think you feel right now and so since we're at the end here together do something for me take a real deep breath and hold on to it in through the nose really trying to get a true lungful at the peak of that breath you'll feel a little shudder feel the fullness of it in your chest then accept the truth that no matter what you are doing you are positively boiling with activity you don't have to be more productive you don't have to prove your worth to anyone i think it's just cool if you hang out for a bit and just be the gorgeous and irrefutable consequence of your own chemistry that's enough work for now i really appreciate your time thank you so much [Music] hey as always thanks so much for making it to the end here if you like this video please consider joining my supporters over at patreon every little bit helps to get more of these videos out more quickly in 2021 this channel will expand to new videos every two weeks and a regular live streaming series this is only the beginning of our biochem journey together join us at patreon.comclockworkshow meanwhile it is incredibly hard to get an accurate view of an atp synthase in this amount of time and in only 2d there are so many amazing additional resources you can check out and really explore atp synthase and see how it works in three dimensions which is where the real magic is and the real nerdum happens i've linked all the sources i used for this video over at my twitter handle at this underscore clockwork the thread is linked in the description get over there and join the conversation if you feel like there was something i should have mentioned about the mechanics of atp synthase or just go there and read what everyone else is saying in terms of the accuracy or in terms of the source material i love all the other animations that exist about atp synthase and i hope what i've done for you is unlock the door to really explore it as opposed to giving you an air quote's definitive resource as always the fact checking in this video is done by my colleague at ans 1998 over on the biocore discord are you a life sciences professional student and or enthusiast looking for the best life sciences community on the internet be sure to check out biochord over at discord gg biology either way thank you so much for hanging out with me to the very end of this video as always i like to leave you with peace love and conformational changes everyone be well thank you so much