WEBVTT 00:00:00.390 --> 00:00:03.370 What I want to do in this video is try to understand how 00:00:03.370 --> 00:00:07.960 two proteins can interact with each other in conjunction with 00:00:07.960 --> 00:00:12.210 ATP to actually produce mechanical motion. 00:00:12.210 --> 00:00:15.320 And the reason why I want to do this-- one, it occurs 00:00:15.320 --> 00:00:17.570 outside of muscle cells as well, but this is really going 00:00:17.570 --> 00:00:20.025 to be the first video on really how muscles work. 00:00:20.025 --> 00:00:23.310 And then we'll talk about how nerves actually stimulate 00:00:23.310 --> 00:00:24.080 muscles to work. 00:00:24.080 --> 00:00:26.580 So it'll all build up from this video. 00:00:26.580 --> 00:00:30.000 So what I've done here is I've copy and pasted two images of 00:00:30.000 --> 00:00:31.480 proteins from Wikipedia. 00:00:31.480 --> 00:00:34.470 This is myosin. 00:00:34.470 --> 00:00:37.110 It's actually myosin II because you actually have two 00:00:37.110 --> 00:00:39.410 strands of the myosin protein. 00:00:39.410 --> 00:00:42.150 They're interwound around each other so you can see it's this 00:00:42.150 --> 00:00:46.040 very complex looking protein or enzyme, however you want to 00:00:46.040 --> 00:00:46.696 talk about it. 00:00:46.696 --> 00:00:48.430 I'll tell you why it's called an enzyme-- because it 00:00:48.430 --> 00:00:53.030 actually helps react ATP into ADP and phosphate groups. 00:00:53.030 --> 00:00:55.460 So that's why it's called an ATPase. 00:00:55.460 --> 00:00:59.150 It's a subclass of the ATPase enzymes. 00:00:59.150 --> 00:01:02.530 This right here is actin. 00:01:02.530 --> 00:01:06.850 What we're going to see in this video is how myosin 00:01:06.850 --> 00:01:10.920 essentially uses the ATP to essentially crawl along. 00:01:10.920 --> 00:01:13.830 You can almost view it as an actin rope and that's what 00:01:13.830 --> 00:01:15.790 creates mechanical energy. 00:01:15.790 --> 00:01:16.490 So let me draw it. 00:01:16.490 --> 00:01:19.240 I'll actually draw it on this actin right here. 00:01:19.240 --> 00:01:23.280 So let's say we have one of these myosin heads. 00:01:23.280 --> 00:01:25.740 So when I say a myosin head, this is one of the myosin 00:01:25.740 --> 00:01:29.140 heads right here and then it's connected, it's interwound, 00:01:29.140 --> 00:01:30.060 it's woven around. 00:01:30.060 --> 00:01:32.630 This is the other one and it winds around that way. 00:01:32.630 --> 00:01:33.900 Now let's just say we're just dealing with one 00:01:33.900 --> 00:01:35.730 of the myosin heads. 00:01:35.730 --> 00:01:37.050 Let's say it's in this position. 00:01:37.050 --> 00:01:39.450 Let me see how well I can draw it. 00:01:39.450 --> 00:01:44.370 Let's say it starts off in a position that looks like that 00:01:44.370 --> 00:01:48.650 and then this is kind of the tail part that connects to 00:01:48.650 --> 00:01:50.480 some other structural and we'll talk about that in more 00:01:50.480 --> 00:01:53.580 detail, but this is my myosin head right there in its 00:01:53.580 --> 00:01:56.490 starting position, not doing anything. 00:01:56.490 --> 00:02:01.990 Now, ATP can come along and bond to this myosin head, this 00:02:01.990 --> 00:02:05.940 enzyme, this protein, this ATPase enzyme. 00:02:05.940 --> 00:02:09.210 So let me draw some ATP. 00:02:09.210 --> 00:02:12.820 So ATP comes along and bonds to this guy right here. 00:02:12.820 --> 00:02:14.850 Let's say that's the-- and it's not going to be this big 00:02:14.850 --> 00:02:16.940 relative to the protein, but this is just to 00:02:16.940 --> 00:02:18.240 give you the idea. 00:02:18.240 --> 00:02:24.120 So soon as the ATP binds to its appropriate site on this 00:02:24.120 --> 00:02:28.400 enzyme or protein, the enzyme, it detaches from the actin. 00:02:28.400 --> 00:02:31.520 So let me write this down. 00:02:31.520 --> 00:02:44.560 So one, ATP binds to myosin head and as soon as that 00:02:44.560 --> 00:02:58.390 happens, that causes the myosin to release actin. 00:02:58.390 --> 00:02:59.720 So that's step one. 00:02:59.720 --> 00:03:03.050 So I start it off with this guy just touching the actin, 00:03:03.050 --> 00:03:05.570 the ATP comes, and it gets released. 00:03:05.570 --> 00:03:09.570 So in the next step-- so after that step, it's going to look 00:03:09.570 --> 00:03:10.815 something like this-- and I want to draw 00:03:10.815 --> 00:03:11.990 it in the same place. 00:03:11.990 --> 00:03:13.300 After the next step, it's going to look 00:03:13.300 --> 00:03:14.810 something like this. 00:03:14.810 --> 00:03:16.060 It will have released. 00:03:19.910 --> 00:03:25.160 So now it looks something like that and you have the ATP 00:03:25.160 --> 00:03:26.870 attached to it still. 00:03:26.870 --> 00:03:28.970 I know it might be a little bit convoluted when I keep 00:03:28.970 --> 00:03:30.450 writing over the same thing, but you have the 00:03:30.450 --> 00:03:31.610 ATP attached to it. 00:03:31.610 --> 00:03:35.320 Now the next step-- the ATP hydrolizes, the phosphate gets 00:03:35.320 --> 00:03:36.430 pulled off of it. 00:03:36.430 --> 00:03:39.330 This is an ATPase enzyme. 00:03:39.330 --> 00:03:40.320 That's what it does. 00:03:40.320 --> 00:03:41.570 Let me write that down. 00:03:54.250 --> 00:03:58.670 And what that does, that releases the energy to cock 00:03:58.670 --> 00:04:03.030 this myosin protein into kind of a high energy state. 00:04:03.030 --> 00:04:05.370 So let me do step two. 00:04:05.370 --> 00:04:08.310 This thing-- it gets hydrolized. 00:04:08.310 --> 00:04:09.250 It releases energy. 00:04:09.250 --> 00:04:13.500 We know that ATP is the energy currency of biological 00:04:13.500 --> 00:04:17.290 systems. So it releases energy. 00:04:17.290 --> 00:04:19.579 I'm drawing it as a little spark or explosion, but you 00:04:19.579 --> 00:04:23.010 can really imagine it's changing the conformation of-- 00:04:23.010 --> 00:04:26.540 it kind of spring-loads this protein right here to go into 00:04:26.540 --> 00:04:29.750 a state so it's ready to crawl along the myosin. 00:04:29.750 --> 00:04:36.500 So in step two-- plus energy, energy and then this-- you can 00:04:36.500 --> 00:04:44.500 say it cocks the myosin protein or 00:04:44.500 --> 00:04:47.410 enzyme to high energy. 00:04:47.410 --> 00:04:50.940 You can imagine it winds the spring, or loads the spring. 00:04:57.650 --> 00:05:01.820 And conformation for proteins just mean shape. 00:05:01.820 --> 00:05:05.970 So step two-- what happens is the phosphate group gets-- 00:05:05.970 --> 00:05:08.830 they're still attached, but it gets detached from 00:05:08.830 --> 00:05:09.950 the rest of the ATP. 00:05:09.950 --> 00:05:12.770 So that becomes ADP and that energy changes the 00:05:12.770 --> 00:05:16.420 conformation so that this protein now goes into a 00:05:16.420 --> 00:05:19.230 position that looks like this. 00:05:19.230 --> 00:05:23.545 So this is where we end up at the end of step two. 00:05:23.545 --> 00:05:27.490 Let me make sure I do it right. 00:05:27.490 --> 00:05:29.130 So at the end of step two, it might look 00:05:29.130 --> 00:05:30.380 something like this. 00:05:36.860 --> 00:05:39.930 So the end of step two, the protein looks 00:05:39.930 --> 00:05:40.560 something like this. 00:05:40.560 --> 00:05:42.260 This is in its cocked position. 00:05:42.260 --> 00:05:43.670 It has a lot of energy right now. 00:05:43.670 --> 00:05:46.620 It's wound up in this position. 00:05:46.620 --> 00:05:49.500 You still have your ADP. 00:05:49.500 --> 00:05:52.810 You still have your-- that's your adenosine and let's say 00:05:52.810 --> 00:05:56.780 you have your two phosphate groups on the ADP and you 00:05:56.780 --> 00:06:00.560 still have one phosphate group right there. 00:06:00.560 --> 00:06:04.490 Now, when that phosphate group releases-- so let me write 00:06:04.490 --> 00:06:06.040 this as step three. 00:06:06.040 --> 00:06:08.380 Remember, when we started, we were just sitting here. 00:06:08.380 --> 00:06:12.190 The ATP binds on step one-- actually, it does definitely 00:06:12.190 --> 00:06:16.440 bind, at the end of step one, that causes the myosin protein 00:06:16.440 --> 00:06:17.880 to get released. 00:06:17.880 --> 00:06:22.060 Then after step one, we naturally have step two. 00:06:22.060 --> 00:06:25.470 The ATP hydrolyzes into ADP phosphate. 00:06:25.470 --> 00:06:29.850 That releases energy and that allows the myosin protein to 00:06:29.850 --> 00:06:33.230 get cocked into this high energy position and kind of 00:06:33.230 --> 00:06:37.620 attach, you can think of it, to the next rung 00:06:37.620 --> 00:06:39.480 of our actin filament. 00:06:39.480 --> 00:06:42.965 Now we're in a high energy state. 00:06:47.160 --> 00:06:49.700 In step three, the phosphate releases. 00:06:57.750 --> 00:07:01.980 The phosphate is released from myosin in step three. 00:07:01.980 --> 00:07:03.170 That's step three right there. 00:07:03.170 --> 00:07:05.260 That's a phosphate group being released. 00:07:05.260 --> 00:07:08.320 And what this does is, this releases that energy of that 00:07:08.320 --> 00:07:14.150 cocked position and it causes this myosin protein 00:07:14.150 --> 00:07:16.290 to push on the actin. 00:07:16.290 --> 00:07:18.730 This is the power stroke, if you imagine in an engine. 00:07:18.730 --> 00:07:21.070 This is what's causing the mechanical movement. 00:07:21.070 --> 00:07:23.390 So when the phosphate group is actually released-- remember, 00:07:23.390 --> 00:07:25.470 the original release is when you take 00:07:25.470 --> 00:07:27.430 ATP to ADP in a phosphate. 00:07:27.430 --> 00:07:30.030 That put it in this spring-loaded position. 00:07:30.030 --> 00:07:32.925 When the phosphate releases it, this releases the spring. 00:07:41.090 --> 00:07:43.430 And what that does is it pushes on the actin filament. 00:07:49.930 --> 00:07:51.720 So you could view this as the power stroke. 00:07:51.720 --> 00:07:53.750 We're actually creating mechanical energy. 00:07:53.750 --> 00:07:56.130 So depending on which one you want to view as fixed-- if you 00:07:56.130 --> 00:07:58.930 view the actin as fixed, whatever myosin is attached to 00:07:58.930 --> 00:08:00.360 it would move to the left. 00:08:00.360 --> 00:08:04.530 If you imagine the myosin being fixed, the actin and 00:08:04.530 --> 00:08:07.190 whatever it's attached to would move to the right, 00:08:07.190 --> 00:08:07.900 either way. 00:08:07.900 --> 00:08:09.540 But this is where we fundamentally 00:08:09.540 --> 00:08:10.950 get the muscle action. 00:08:10.950 --> 00:08:16.295 And then step four-- you have the ADP released. 00:08:21.170 --> 00:08:25.960 And then we're exactly where we were before we did step 00:08:25.960 --> 00:08:29.260 one, except we're just one rung further to the left on 00:08:29.260 --> 00:08:31.890 the actin molecule. 00:08:31.890 --> 00:08:33.530 So to me, this is pretty amazing. 00:08:33.530 --> 00:08:38.000 We actually are seeing how ATP energy can be used to-- we're 00:08:38.000 --> 00:08:47.570 going from chemical energy or bond energy in ATP to 00:08:47.570 --> 00:08:48.820 mechanical energy. 00:08:53.060 --> 00:08:55.080 For me, that's amazing because when I first learned about 00:08:55.080 --> 00:08:58.640 ATP-- people say, you use ATP to do everything in your cells 00:08:58.640 --> 00:08:59.650 and contract muscles. 00:08:59.650 --> 00:09:02.350 Well, gee, how do you go from bond energy to actually 00:09:02.350 --> 00:09:04.850 contracting things, to actually doing what we see in 00:09:04.850 --> 00:09:07.010 our everyday world as mechanical energy? 00:09:07.010 --> 00:09:09.390 And this is really where it all occurs. 00:09:09.390 --> 00:09:12.140 This is really the core issue that's going on here. 00:09:12.140 --> 00:09:14.110 And you have to say, well, gee, how this thing change 00:09:14.110 --> 00:09:15.290 shape and all that? 00:09:15.290 --> 00:09:17.320 And you have to remember, these proteins, based on 00:09:17.320 --> 00:09:19.240 what's bonded to it and what's not bonded to 00:09:19.240 --> 00:09:20.260 it, they change shape. 00:09:20.260 --> 00:09:23.810 And some of those shapes take more energy to attain, and 00:09:23.810 --> 00:09:26.610 then if you do the right things, that energy can be 00:09:26.610 --> 00:09:29.440 released and then it can push another protein. 00:09:29.440 --> 00:09:30.920 But I find this just fascinating. 00:09:30.920 --> 00:09:34.100 And now we can build up from this actin and myosin 00:09:34.100 --> 00:09:37.930 interactions to understand how muscles actually work.