1 00:00:00,000 --> 00:00:00,390 2 00:00:00,390 --> 00:00:03,370 What I want to do in this video is try to understand how 3 00:00:03,370 --> 00:00:07,960 two proteins can interact with each other in conjunction with 4 00:00:07,960 --> 00:00:12,210 ATP to actually produce mechanical motion. 5 00:00:12,210 --> 00:00:15,320 And the reason why I want to do this-- one, it occurs 6 00:00:15,320 --> 00:00:17,570 outside of muscle cells as well, but this is really going 7 00:00:17,570 --> 00:00:20,025 to be the first video on really how muscles work. 8 00:00:20,025 --> 00:00:23,310 And then we'll talk about how nerves actually stimulate 9 00:00:23,310 --> 00:00:24,080 muscles to work. 10 00:00:24,080 --> 00:00:26,580 So it'll all build up from this video. 11 00:00:26,580 --> 00:00:30,000 So what I've done here is I've copy and pasted two images of 12 00:00:30,000 --> 00:00:31,480 proteins from Wikipedia. 13 00:00:31,480 --> 00:00:34,470 This is myosin. 14 00:00:34,470 --> 00:00:37,110 It's actually myosin II because you actually have two 15 00:00:37,110 --> 00:00:39,410 strands of the myosin protein. 16 00:00:39,410 --> 00:00:42,150 They're interwound around each other so you can see it's this 17 00:00:42,150 --> 00:00:46,040 very complex looking protein or enzyme, however you want to 18 00:00:46,040 --> 00:00:46,696 talk about it. 19 00:00:46,696 --> 00:00:48,430 I'll tell you why it's called an enzyme-- because it 20 00:00:48,430 --> 00:00:53,030 actually helps react ATP into ADP and phosphate groups. 21 00:00:53,030 --> 00:00:55,460 So that's why it's called an ATPase. 22 00:00:55,460 --> 00:00:59,150 It's a subclass of the ATPase enzymes. 23 00:00:59,150 --> 00:01:02,530 This right here is actin. 24 00:01:02,530 --> 00:01:06,850 What we're going to see in this video is how myosin 25 00:01:06,850 --> 00:01:10,920 essentially uses the ATP to essentially crawl along. 26 00:01:10,920 --> 00:01:13,830 You can almost view it as an actin rope and that's what 27 00:01:13,830 --> 00:01:15,790 creates mechanical energy. 28 00:01:15,790 --> 00:01:16,490 So let me draw it. 29 00:01:16,490 --> 00:01:19,240 I'll actually draw it on this actin right here. 30 00:01:19,240 --> 00:01:23,280 So let's say we have one of these myosin heads. 31 00:01:23,280 --> 00:01:25,740 So when I say a myosin head, this is one of the myosin 32 00:01:25,740 --> 00:01:29,140 heads right here and then it's connected, it's interwound, 33 00:01:29,140 --> 00:01:30,060 it's woven around. 34 00:01:30,060 --> 00:01:32,630 This is the other one and it winds around that way. 35 00:01:32,630 --> 00:01:33,900 Now let's just say we're just dealing with one 36 00:01:33,900 --> 00:01:35,730 of the myosin heads. 37 00:01:35,730 --> 00:01:37,050 Let's say it's in this position. 38 00:01:37,050 --> 00:01:39,450 Let me see how well I can draw it. 39 00:01:39,450 --> 00:01:44,370 Let's say it starts off in a position that looks like that 40 00:01:44,370 --> 00:01:48,650 and then this is kind of the tail part that connects to 41 00:01:48,650 --> 00:01:50,480 some other structural and we'll talk about that in more 42 00:01:50,480 --> 00:01:53,580 detail, but this is my myosin head right there in its 43 00:01:53,580 --> 00:01:56,490 starting position, not doing anything. 44 00:01:56,490 --> 00:02:01,990 Now, ATP can come along and bond to this myosin head, this 45 00:02:01,990 --> 00:02:05,940 enzyme, this protein, this ATPase enzyme. 46 00:02:05,940 --> 00:02:09,210 So let me draw some ATP. 47 00:02:09,210 --> 00:02:12,820 So ATP comes along and bonds to this guy right here. 48 00:02:12,820 --> 00:02:14,850 Let's say that's the-- and it's not going to be this big 49 00:02:14,850 --> 00:02:16,940 relative to the protein, but this is just to 50 00:02:16,940 --> 00:02:18,240 give you the idea. 51 00:02:18,240 --> 00:02:24,120 So soon as the ATP binds to its appropriate site on this 52 00:02:24,120 --> 00:02:28,400 enzyme or protein, the enzyme, it detaches from the actin. 53 00:02:28,400 --> 00:02:31,520 So let me write this down. 54 00:02:31,520 --> 00:02:44,560 So one, ATP binds to myosin head and as soon as that 55 00:02:44,560 --> 00:02:58,390 happens, that causes the myosin to release actin. 56 00:02:58,390 --> 00:02:59,720 So that's step one. 57 00:02:59,720 --> 00:03:03,050 So I start it off with this guy just touching the actin, 58 00:03:03,050 --> 00:03:05,570 the ATP comes, and it gets released. 59 00:03:05,570 --> 00:03:09,570 So in the next step-- so after that step, it's going to look 60 00:03:09,570 --> 00:03:10,815 something like this-- and I want to draw 61 00:03:10,815 --> 00:03:11,990 it in the same place. 62 00:03:11,990 --> 00:03:13,300 After the next step, it's going to look 63 00:03:13,300 --> 00:03:14,810 something like this. 64 00:03:14,810 --> 00:03:16,060 It will have released. 65 00:03:16,060 --> 00:03:19,910 66 00:03:19,910 --> 00:03:25,160 So now it looks something like that and you have the ATP 67 00:03:25,160 --> 00:03:26,870 attached to it still. 68 00:03:26,870 --> 00:03:28,970 I know it might be a little bit convoluted when I keep 69 00:03:28,970 --> 00:03:30,450 writing over the same thing, but you have the 70 00:03:30,450 --> 00:03:31,610 ATP attached to it. 71 00:03:31,610 --> 00:03:35,320 Now the next step-- the ATP hydrolizes, the phosphate gets 72 00:03:35,320 --> 00:03:36,430 pulled off of it. 73 00:03:36,430 --> 00:03:39,330 This is an ATPase enzyme. 74 00:03:39,330 --> 00:03:40,320 That's what it does. 75 00:03:40,320 --> 00:03:41,570 Let me write that down. 76 00:03:41,570 --> 00:03:54,250 77 00:03:54,250 --> 00:03:58,670 And what that does, that releases the energy to cock 78 00:03:58,670 --> 00:04:03,030 this myosin protein into kind of a high energy state. 79 00:04:03,030 --> 00:04:05,370 So let me do step two. 80 00:04:05,370 --> 00:04:08,310 This thing-- it gets hydrolized. 81 00:04:08,310 --> 00:04:09,250 It releases energy. 82 00:04:09,250 --> 00:04:13,500 We know that ATP is the energy currency of biological 83 00:04:13,500 --> 00:04:17,290 systems. So it releases energy. 84 00:04:17,290 --> 00:04:19,579 I'm drawing it as a little spark or explosion, but you 85 00:04:19,579 --> 00:04:23,010 can really imagine it's changing the confirmation of-- 86 00:04:23,010 --> 00:04:26,540 it kind of spring-loads this protein right here to go into 87 00:04:26,540 --> 00:04:29,750 a state so it's ready to crawl along the myosin. 88 00:04:29,750 --> 00:04:36,500 So in step two-- plus energy, energy and then this-- you can 89 00:04:36,500 --> 00:04:44,500 say it cocks the myosin protein or 90 00:04:44,500 --> 00:04:47,410 enzyme to high energy. 91 00:04:47,410 --> 00:04:50,940 You can imagine it winds the spring, or loads the spring. 92 00:04:50,940 --> 00:04:57,650 93 00:04:57,650 --> 00:05:01,820 And confirmation for proteins just mean shape. 94 00:05:01,820 --> 00:05:05,970 So step two-- what happens is the phosphate group gets-- 95 00:05:05,970 --> 00:05:08,830 they're still attached, but it gets detached from 96 00:05:08,830 --> 00:05:09,950 the rest of the ATP. 97 00:05:09,950 --> 00:05:12,770 So that becomes ADP and that energy changes the 98 00:05:12,770 --> 00:05:16,420 confirmation so that this protein now goes into a 99 00:05:16,420 --> 00:05:19,230 position that looks like this. 100 00:05:19,230 --> 00:05:23,545 So this is where we end up at the end of step two. 101 00:05:23,545 --> 00:05:27,490 Let me make sure I do it right. 102 00:05:27,490 --> 00:05:29,130 So at the end of step two, it might look 103 00:05:29,130 --> 00:05:30,380 something like this. 104 00:05:30,380 --> 00:05:36,860 105 00:05:36,860 --> 00:05:39,930 So the end of step two, the protein looks 106 00:05:39,930 --> 00:05:40,560 something like this. 107 00:05:40,560 --> 00:05:42,260 This is in its cocked position. 108 00:05:42,260 --> 00:05:43,670 It has a lot of energy right now. 109 00:05:43,670 --> 00:05:46,620 It's wound up in this position. 110 00:05:46,620 --> 00:05:49,500 You still have your ADP. 111 00:05:49,500 --> 00:05:52,810 You still have your-- that's your adenosine and let's say 112 00:05:52,810 --> 00:05:56,780 you have your two phosphate groups on the ADP and you 113 00:05:56,780 --> 00:06:00,560 still have one phosphate group right there. 114 00:06:00,560 --> 00:06:04,490 Now, when that phosphate group releases-- so let me write 115 00:06:04,490 --> 00:06:06,040 this as step three. 116 00:06:06,040 --> 00:06:08,380 Remember, when we started, we were just sitting here. 117 00:06:08,380 --> 00:06:12,190 The ATP binds on step one-- actually, it does definitely 118 00:06:12,190 --> 00:06:16,440 bind, at the end of step one, that causes the myosin protein 119 00:06:16,440 --> 00:06:17,880 to get released. 120 00:06:17,880 --> 00:06:22,060 Then after step one, we naturally have step two. 121 00:06:22,060 --> 00:06:25,470 The ATP hydrolyzes into ADP phosphate. 122 00:06:25,470 --> 00:06:29,850 That releases energy and that allows the myosin protein to 123 00:06:29,850 --> 00:06:33,230 get cocked into this high energy position and kind of 124 00:06:33,230 --> 00:06:37,620 attach, you can think of it, to the next rung 125 00:06:37,620 --> 00:06:39,480 of our actin filament. 126 00:06:39,480 --> 00:06:42,965 Now we're in a high energy state. 127 00:06:42,965 --> 00:06:47,160 128 00:06:47,160 --> 00:06:49,700 In step three, the phosphate releases. 129 00:06:49,700 --> 00:06:57,750 130 00:06:57,750 --> 00:07:01,980 The phosphate is released from myosin in step three. 131 00:07:01,980 --> 00:07:03,170 That's step three right there. 132 00:07:03,170 --> 00:07:05,260 That's a phosphate group being released. 133 00:07:05,260 --> 00:07:08,320 And what this does is, this releases that energy of that 134 00:07:08,320 --> 00:07:14,150 cocked position and it causes this myosin protein 135 00:07:14,150 --> 00:07:16,290 to push on the actin. 136 00:07:16,290 --> 00:07:18,730 This is the power stroke, if you imagine in an engine. 137 00:07:18,730 --> 00:07:21,070 This is what's causing the mechanical movement. 138 00:07:21,070 --> 00:07:23,390 So when the phosphate group is actually released-- remember, 139 00:07:23,390 --> 00:07:25,470 the original release is when you take 140 00:07:25,470 --> 00:07:27,430 ATP to ADP in a phosphate. 141 00:07:27,430 --> 00:07:30,030 That put it in this spring-loaded position. 142 00:07:30,030 --> 00:07:32,925 When the phosphate releases it, this releases the spring. 143 00:07:32,925 --> 00:07:41,090 144 00:07:41,090 --> 00:07:43,430 And what that does is it pushes on the actin filament. 145 00:07:43,430 --> 00:07:49,930 146 00:07:49,930 --> 00:07:51,720 So you could view this as the power stroke. 147 00:07:51,720 --> 00:07:53,750 We're actually creating mechanical energy. 148 00:07:53,750 --> 00:07:56,130 So depending on which one you want to view as fixed-- if you 149 00:07:56,130 --> 00:07:58,930 view the actin as fixed, whatever myosin is attached to 150 00:07:58,930 --> 00:08:00,360 it would move to the left. 151 00:08:00,360 --> 00:08:04,530 If you imagine the myosin being fixed, the actin and 152 00:08:04,530 --> 00:08:07,190 whatever it's attached to would move to the right, 153 00:08:07,190 --> 00:08:07,900 either way. 154 00:08:07,900 --> 00:08:09,540 But this is where we fundamentally 155 00:08:09,540 --> 00:08:10,950 get the muscle action. 156 00:08:10,950 --> 00:08:16,295 And then step four-- you have the ADP released. 157 00:08:16,295 --> 00:08:21,170 158 00:08:21,170 --> 00:08:25,960 And then we're exactly where we were before we did step 159 00:08:25,960 --> 00:08:29,260 one, except we're just one rung further to the left on 160 00:08:29,260 --> 00:08:31,890 the actin molecule. 161 00:08:31,890 --> 00:08:33,530 So to me, this is pretty amazing. 162 00:08:33,530 --> 00:08:38,000 We actually are seeing how ATP energy can be used to-- we're 163 00:08:38,000 --> 00:08:47,570 going from chemical energy or bond energy in ATP to 164 00:08:47,570 --> 00:08:48,820 mechanical energy. 165 00:08:48,820 --> 00:08:53,060 166 00:08:53,060 --> 00:08:55,080 For me, that's amazing because when I first learned about 167 00:08:55,080 --> 00:08:58,640 ATP-- people say, you use ATP to do everything in your cells 168 00:08:58,640 --> 00:08:59,650 and contract muscles. 169 00:08:59,650 --> 00:09:02,350 Well, gee, how do you go from bond energy to actually 170 00:09:02,350 --> 00:09:04,850 contracting things, to actually doing what we see in 171 00:09:04,850 --> 00:09:07,010 our everyday world as mechanical energy? 172 00:09:07,010 --> 00:09:09,390 And this is really where it all occurs. 173 00:09:09,390 --> 00:09:12,140 This is really the core issue that's going on here. 174 00:09:12,140 --> 00:09:14,110 And you have to say, well, gee, how this thing change 175 00:09:14,110 --> 00:09:15,290 shape and all that? 176 00:09:15,290 --> 00:09:17,320 And you have to remember, these proteins, based on 177 00:09:17,320 --> 00:09:19,240 what's bonded to it and what's not bonded to 178 00:09:19,240 --> 00:09:20,260 it, they change shape. 179 00:09:20,260 --> 00:09:23,810 And some of those shapes take more energy to attain, and 180 00:09:23,810 --> 00:09:26,610 then if you do the right things, that energy can be 181 00:09:26,610 --> 00:09:29,440 released and then it can push another protein. 182 00:09:29,440 --> 00:09:30,920 But I find this just fascinating. 183 00:09:30,920 --> 00:09:34,100 And now we can build up from this actin and myosin 184 00:09:34,100 --> 00:09:37,930 interactions to understand how muscles actually work.