[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:00.39,0:00:03.37,Default,,0000,0000,0000,,What I want to do in this video\Nis try to understand how
Dialogue: 0,0:00:03.37,0:00:07.96,Default,,0000,0000,0000,,two proteins can interact with\Neach other in conjunction with
Dialogue: 0,0:00:07.96,0:00:12.21,Default,,0000,0000,0000,,ATP to actually produce\Nmechanical motion.
Dialogue: 0,0:00:12.21,0:00:15.32,Default,,0000,0000,0000,,And the reason why I want to\Ndo this-- one, it occurs
Dialogue: 0,0:00:15.32,0:00:17.57,Default,,0000,0000,0000,,outside of muscle cells as well,\Nbut this is really going
Dialogue: 0,0:00:17.57,0:00:20.02,Default,,0000,0000,0000,,to be the first video on really\Nhow muscles work.
Dialogue: 0,0:00:20.02,0:00:23.31,Default,,0000,0000,0000,,And then we'll talk about how\Nnerves actually stimulate
Dialogue: 0,0:00:23.31,0:00:24.08,Default,,0000,0000,0000,,muscles to work.
Dialogue: 0,0:00:24.08,0:00:26.58,Default,,0000,0000,0000,,So it'll all build up\Nfrom this video.
Dialogue: 0,0:00:26.58,0:00:30.00,Default,,0000,0000,0000,,So what I've done here is I've\Ncopy and pasted two images of
Dialogue: 0,0:00:30.00,0:00:31.48,Default,,0000,0000,0000,,proteins from Wikipedia.
Dialogue: 0,0:00:31.48,0:00:34.47,Default,,0000,0000,0000,,This is myosin.
Dialogue: 0,0:00:34.47,0:00:37.11,Default,,0000,0000,0000,,It's actually myosin II because\Nyou actually have two
Dialogue: 0,0:00:37.11,0:00:39.41,Default,,0000,0000,0000,,strands of the myosin protein.
Dialogue: 0,0:00:39.41,0:00:42.15,Default,,0000,0000,0000,,They're interwound around each\Nother so you can see it's this
Dialogue: 0,0:00:42.15,0:00:46.04,Default,,0000,0000,0000,,very complex looking protein or\Nenzyme, however you want to
Dialogue: 0,0:00:46.04,0:00:46.70,Default,,0000,0000,0000,,talk about it.
Dialogue: 0,0:00:46.70,0:00:48.43,Default,,0000,0000,0000,,I'll tell you why it's called\Nan enzyme-- because it
Dialogue: 0,0:00:48.43,0:00:53.03,Default,,0000,0000,0000,,actually helps react ATP into\NADP and phosphate groups.
Dialogue: 0,0:00:53.03,0:00:55.46,Default,,0000,0000,0000,,So that's why it's\Ncalled an ATPase.
Dialogue: 0,0:00:55.46,0:00:59.15,Default,,0000,0000,0000,,It's a subclass of the\NATPase enzymes.
Dialogue: 0,0:00:59.15,0:01:02.53,Default,,0000,0000,0000,,This right here is actin.
Dialogue: 0,0:01:02.53,0:01:06.85,Default,,0000,0000,0000,,What we're going to see in\Nthis video is how myosin
Dialogue: 0,0:01:06.85,0:01:10.92,Default,,0000,0000,0000,,essentially uses the ATP to\Nessentially crawl along.
Dialogue: 0,0:01:10.92,0:01:13.83,Default,,0000,0000,0000,,You can almost view it as an\Nactin rope and that's what
Dialogue: 0,0:01:13.83,0:01:15.79,Default,,0000,0000,0000,,creates mechanical energy.
Dialogue: 0,0:01:15.79,0:01:16.49,Default,,0000,0000,0000,,So let me draw it.
Dialogue: 0,0:01:16.49,0:01:19.24,Default,,0000,0000,0000,,I'll actually draw it on\Nthis actin right here.
Dialogue: 0,0:01:19.24,0:01:23.28,Default,,0000,0000,0000,,So let's say we have one\Nof these myosin heads.
Dialogue: 0,0:01:23.28,0:01:25.74,Default,,0000,0000,0000,,So when I say a myosin head,\Nthis is one of the myosin
Dialogue: 0,0:01:25.74,0:01:29.14,Default,,0000,0000,0000,,heads right here and then it's\Nconnected, it's interwound,
Dialogue: 0,0:01:29.14,0:01:30.06,Default,,0000,0000,0000,,it's woven around.
Dialogue: 0,0:01:30.06,0:01:32.63,Default,,0000,0000,0000,,This is the other one and it\Nwinds around that way.
Dialogue: 0,0:01:32.63,0:01:33.90,Default,,0000,0000,0000,,Now let's just say we're\Njust dealing with one
Dialogue: 0,0:01:33.90,0:01:35.73,Default,,0000,0000,0000,,of the myosin heads.
Dialogue: 0,0:01:35.73,0:01:37.05,Default,,0000,0000,0000,,Let's say it's in\Nthis position.
Dialogue: 0,0:01:37.05,0:01:39.45,Default,,0000,0000,0000,,Let me see how well\NI can draw it.
Dialogue: 0,0:01:39.45,0:01:44.37,Default,,0000,0000,0000,,Let's say it starts off in a\Nposition that looks like that
Dialogue: 0,0:01:44.37,0:01:48.65,Default,,0000,0000,0000,,and then this is kind of the\Ntail part that connects to
Dialogue: 0,0:01:48.65,0:01:50.48,Default,,0000,0000,0000,,some other structural and we'll\Ntalk about that in more
Dialogue: 0,0:01:50.48,0:01:53.58,Default,,0000,0000,0000,,detail, but this is my myosin\Nhead right there in its
Dialogue: 0,0:01:53.58,0:01:56.49,Default,,0000,0000,0000,,starting position, not\Ndoing anything.
Dialogue: 0,0:01:56.49,0:02:01.99,Default,,0000,0000,0000,,Now, ATP can come along and bond\Nto this myosin head, this
Dialogue: 0,0:02:01.99,0:02:05.94,Default,,0000,0000,0000,,enzyme, this protein,\Nthis ATPase enzyme.
Dialogue: 0,0:02:05.94,0:02:09.21,Default,,0000,0000,0000,,So let me draw some ATP.
Dialogue: 0,0:02:09.21,0:02:12.82,Default,,0000,0000,0000,,So ATP comes along and bonds\Nto this guy right here.
Dialogue: 0,0:02:12.82,0:02:14.85,Default,,0000,0000,0000,,Let's say that's the-- and it's\Nnot going to be this big
Dialogue: 0,0:02:14.85,0:02:16.94,Default,,0000,0000,0000,,relative to the protein,\Nbut this is just to
Dialogue: 0,0:02:16.94,0:02:18.24,Default,,0000,0000,0000,,give you the idea.
Dialogue: 0,0:02:18.24,0:02:24.12,Default,,0000,0000,0000,,So soon as the ATP binds to its\Nappropriate site on this
Dialogue: 0,0:02:24.12,0:02:28.40,Default,,0000,0000,0000,,enzyme or protein, the enzyme,\Nit detaches from the actin.
Dialogue: 0,0:02:28.40,0:02:31.52,Default,,0000,0000,0000,,So let me write this down.
Dialogue: 0,0:02:31.52,0:02:44.56,Default,,0000,0000,0000,,So one, ATP binds to myosin\Nhead and as soon as that
Dialogue: 0,0:02:44.56,0:02:58.39,Default,,0000,0000,0000,,happens, that causes the myosin\Nto release actin.
Dialogue: 0,0:02:58.39,0:02:59.72,Default,,0000,0000,0000,,So that's step one.
Dialogue: 0,0:02:59.72,0:03:03.05,Default,,0000,0000,0000,,So I start it off with this guy\Njust touching the actin,
Dialogue: 0,0:03:03.05,0:03:05.57,Default,,0000,0000,0000,,the ATP comes, and\Nit gets released.
Dialogue: 0,0:03:05.57,0:03:09.57,Default,,0000,0000,0000,,So in the next step-- so after\Nthat step, it's going to look
Dialogue: 0,0:03:09.57,0:03:10.82,Default,,0000,0000,0000,,something like this--\Nand I want to draw
Dialogue: 0,0:03:10.82,0:03:11.99,Default,,0000,0000,0000,,it in the same place.
Dialogue: 0,0:03:11.99,0:03:13.30,Default,,0000,0000,0000,,After the next step,\Nit's going to look
Dialogue: 0,0:03:13.30,0:03:14.81,Default,,0000,0000,0000,,something like this.
Dialogue: 0,0:03:14.81,0:03:16.06,Default,,0000,0000,0000,,It will have released.
Dialogue: 0,0:03:19.91,0:03:25.16,Default,,0000,0000,0000,,So now it looks something like\Nthat and you have the ATP
Dialogue: 0,0:03:25.16,0:03:26.87,Default,,0000,0000,0000,,attached to it still.
Dialogue: 0,0:03:26.87,0:03:28.97,Default,,0000,0000,0000,,I know it might be a little\Nbit convoluted when I keep
Dialogue: 0,0:03:28.97,0:03:30.45,Default,,0000,0000,0000,,writing over the same thing,\Nbut you have the
Dialogue: 0,0:03:30.45,0:03:31.61,Default,,0000,0000,0000,,ATP attached to it.
Dialogue: 0,0:03:31.61,0:03:35.32,Default,,0000,0000,0000,,Now the next step-- the ATP\Nhydrolizes, the phosphate gets
Dialogue: 0,0:03:35.32,0:03:36.43,Default,,0000,0000,0000,,pulled off of it.
Dialogue: 0,0:03:36.43,0:03:39.33,Default,,0000,0000,0000,,This is an ATPase enzyme.
Dialogue: 0,0:03:39.33,0:03:40.32,Default,,0000,0000,0000,,That's what it does.
Dialogue: 0,0:03:40.32,0:03:41.57,Default,,0000,0000,0000,,Let me write that down.
Dialogue: 0,0:03:54.25,0:03:58.67,Default,,0000,0000,0000,,And what that does, that\Nreleases the energy to cock
Dialogue: 0,0:03:58.67,0:04:03.03,Default,,0000,0000,0000,,this myosin protein into kind\Nof a high energy state.
Dialogue: 0,0:04:03.03,0:04:05.37,Default,,0000,0000,0000,,So let me do step two.
Dialogue: 0,0:04:05.37,0:04:08.31,Default,,0000,0000,0000,,This thing-- it gets\Nhydrolized.
Dialogue: 0,0:04:08.31,0:04:09.25,Default,,0000,0000,0000,,It releases energy.
Dialogue: 0,0:04:09.25,0:04:13.50,Default,,0000,0000,0000,,We know that ATP is the energy\Ncurrency of biological
Dialogue: 0,0:04:13.50,0:04:17.29,Default,,0000,0000,0000,,systems. So it releases\Nenergy.
Dialogue: 0,0:04:17.29,0:04:19.58,Default,,0000,0000,0000,,I'm drawing it as a little spark\Nor explosion, but you
Dialogue: 0,0:04:19.58,0:04:23.01,Default,,0000,0000,0000,,can really imagine it's changing\Nthe conformation of--
Dialogue: 0,0:04:23.01,0:04:26.54,Default,,0000,0000,0000,,it kind of spring-loads this\Nprotein right here to go into
Dialogue: 0,0:04:26.54,0:04:29.75,Default,,0000,0000,0000,,a state so it's ready to\Ncrawl along the myosin.
Dialogue: 0,0:04:29.75,0:04:36.50,Default,,0000,0000,0000,,So in step two-- plus energy,\Nenergy and then this-- you can
Dialogue: 0,0:04:36.50,0:04:44.50,Default,,0000,0000,0000,,say it cocks the myosin\Nprotein or
Dialogue: 0,0:04:44.50,0:04:47.41,Default,,0000,0000,0000,,enzyme to high energy.
Dialogue: 0,0:04:47.41,0:04:50.94,Default,,0000,0000,0000,,You can imagine it winds the\Nspring, or loads the spring.
Dialogue: 0,0:04:57.65,0:05:01.82,Default,,0000,0000,0000,,And conformation for proteins\Njust mean shape.
Dialogue: 0,0:05:01.82,0:05:05.97,Default,,0000,0000,0000,,So step two-- what happens is\Nthe phosphate group gets--
Dialogue: 0,0:05:05.97,0:05:08.83,Default,,0000,0000,0000,,they're still attached, but\Nit gets detached from
Dialogue: 0,0:05:08.83,0:05:09.95,Default,,0000,0000,0000,,the rest of the ATP.
Dialogue: 0,0:05:09.95,0:05:12.77,Default,,0000,0000,0000,,So that becomes ADP and that\Nenergy changes the
Dialogue: 0,0:05:12.77,0:05:16.42,Default,,0000,0000,0000,,conformation so that this\Nprotein now goes into a
Dialogue: 0,0:05:16.42,0:05:19.23,Default,,0000,0000,0000,,position that looks like this.
Dialogue: 0,0:05:19.23,0:05:23.54,Default,,0000,0000,0000,,So this is where we end up\Nat the end of step two.
Dialogue: 0,0:05:23.54,0:05:27.49,Default,,0000,0000,0000,,Let me make sure\NI do it right.
Dialogue: 0,0:05:27.49,0:05:29.13,Default,,0000,0000,0000,,So at the end of step\Ntwo, it might look
Dialogue: 0,0:05:29.13,0:05:30.38,Default,,0000,0000,0000,,something like this.
Dialogue: 0,0:05:36.86,0:05:39.93,Default,,0000,0000,0000,,So the end of step two,\Nthe protein looks
Dialogue: 0,0:05:39.93,0:05:40.56,Default,,0000,0000,0000,,something like this.
Dialogue: 0,0:05:40.56,0:05:42.26,Default,,0000,0000,0000,,This is in its cocked\Nposition.
Dialogue: 0,0:05:42.26,0:05:43.67,Default,,0000,0000,0000,,It has a lot of energy\Nright now.
Dialogue: 0,0:05:43.67,0:05:46.62,Default,,0000,0000,0000,,It's wound up in\Nthis position.
Dialogue: 0,0:05:46.62,0:05:49.50,Default,,0000,0000,0000,,You still have your ADP.
Dialogue: 0,0:05:49.50,0:05:52.81,Default,,0000,0000,0000,,You still have your-- that's\Nyour adenosine and let's say
Dialogue: 0,0:05:52.81,0:05:56.78,Default,,0000,0000,0000,,you have your two phosphate\Ngroups on the ADP and you
Dialogue: 0,0:05:56.78,0:06:00.56,Default,,0000,0000,0000,,still have one phosphate\Ngroup right there.
Dialogue: 0,0:06:00.56,0:06:04.49,Default,,0000,0000,0000,,Now, when that phosphate group\Nreleases-- so let me write
Dialogue: 0,0:06:04.49,0:06:06.04,Default,,0000,0000,0000,,this as step three.
Dialogue: 0,0:06:06.04,0:06:08.38,Default,,0000,0000,0000,,Remember, when we started, we\Nwere just sitting here.
Dialogue: 0,0:06:08.38,0:06:12.19,Default,,0000,0000,0000,,The ATP binds on step one--\Nactually, it does definitely
Dialogue: 0,0:06:12.19,0:06:16.44,Default,,0000,0000,0000,,bind, at the end of step one,\Nthat causes the myosin protein
Dialogue: 0,0:06:16.44,0:06:17.88,Default,,0000,0000,0000,,to get released.
Dialogue: 0,0:06:17.88,0:06:22.06,Default,,0000,0000,0000,,Then after step one, we\Nnaturally have step two.
Dialogue: 0,0:06:22.06,0:06:25.47,Default,,0000,0000,0000,,The ATP hydrolyzes into\NADP phosphate.
Dialogue: 0,0:06:25.47,0:06:29.85,Default,,0000,0000,0000,,That releases energy and that\Nallows the myosin protein to
Dialogue: 0,0:06:29.85,0:06:33.23,Default,,0000,0000,0000,,get cocked into this high energy\Nposition and kind of
Dialogue: 0,0:06:33.23,0:06:37.62,Default,,0000,0000,0000,,attach, you can think of\Nit, to the next rung
Dialogue: 0,0:06:37.62,0:06:39.48,Default,,0000,0000,0000,,of our actin filament.
Dialogue: 0,0:06:39.48,0:06:42.96,Default,,0000,0000,0000,,Now we're in a high\Nenergy state.
Dialogue: 0,0:06:47.16,0:06:49.70,Default,,0000,0000,0000,,In step three, the phosphate\Nreleases.
Dialogue: 0,0:06:57.75,0:07:01.98,Default,,0000,0000,0000,,The phosphate is released from\Nmyosin in step three.
Dialogue: 0,0:07:01.98,0:07:03.17,Default,,0000,0000,0000,,That's step three right there.
Dialogue: 0,0:07:03.17,0:07:05.26,Default,,0000,0000,0000,,That's a phosphate group\Nbeing released.
Dialogue: 0,0:07:05.26,0:07:08.32,Default,,0000,0000,0000,,And what this does is, this\Nreleases that energy of that
Dialogue: 0,0:07:08.32,0:07:14.15,Default,,0000,0000,0000,,cocked position and it causes\Nthis myosin protein
Dialogue: 0,0:07:14.15,0:07:16.29,Default,,0000,0000,0000,,to push on the actin.
Dialogue: 0,0:07:16.29,0:07:18.73,Default,,0000,0000,0000,,This is the power stroke, if\Nyou imagine in an engine.
Dialogue: 0,0:07:18.73,0:07:21.07,Default,,0000,0000,0000,,This is what's causing the\Nmechanical movement.
Dialogue: 0,0:07:21.07,0:07:23.39,Default,,0000,0000,0000,,So when the phosphate group is\Nactually released-- remember,
Dialogue: 0,0:07:23.39,0:07:25.47,Default,,0000,0000,0000,,the original release\Nis when you take
Dialogue: 0,0:07:25.47,0:07:27.43,Default,,0000,0000,0000,,ATP to ADP in a phosphate.
Dialogue: 0,0:07:27.43,0:07:30.03,Default,,0000,0000,0000,,That put it in this\Nspring-loaded position.
Dialogue: 0,0:07:30.03,0:07:32.92,Default,,0000,0000,0000,,When the phosphate releases it,\Nthis releases the spring.
Dialogue: 0,0:07:41.09,0:07:43.43,Default,,0000,0000,0000,,And what that does is it pushes\Non the actin filament.
Dialogue: 0,0:07:49.93,0:07:51.72,Default,,0000,0000,0000,,So you could view this\Nas the power stroke.
Dialogue: 0,0:07:51.72,0:07:53.75,Default,,0000,0000,0000,,We're actually creating\Nmechanical energy.
Dialogue: 0,0:07:53.75,0:07:56.13,Default,,0000,0000,0000,,So depending on which one you\Nwant to view as fixed-- if you
Dialogue: 0,0:07:56.13,0:07:58.93,Default,,0000,0000,0000,,view the actin as fixed,\Nwhatever myosin is attached to
Dialogue: 0,0:07:58.93,0:08:00.36,Default,,0000,0000,0000,,it would move to the left.
Dialogue: 0,0:08:00.36,0:08:04.53,Default,,0000,0000,0000,,If you imagine the myosin being\Nfixed, the actin and
Dialogue: 0,0:08:04.53,0:08:07.19,Default,,0000,0000,0000,,whatever it's attached to\Nwould move to the right,
Dialogue: 0,0:08:07.19,0:08:07.90,Default,,0000,0000,0000,,either way.
Dialogue: 0,0:08:07.90,0:08:09.54,Default,,0000,0000,0000,,But this is where\Nwe fundamentally
Dialogue: 0,0:08:09.54,0:08:10.95,Default,,0000,0000,0000,,get the muscle action.
Dialogue: 0,0:08:10.95,0:08:16.30,Default,,0000,0000,0000,,And then step four-- you\Nhave the ADP released.
Dialogue: 0,0:08:21.17,0:08:25.96,Default,,0000,0000,0000,,And then we're exactly where\Nwe were before we did step
Dialogue: 0,0:08:25.96,0:08:29.26,Default,,0000,0000,0000,,one, except we're just one rung\Nfurther to the left on
Dialogue: 0,0:08:29.26,0:08:31.89,Default,,0000,0000,0000,,the actin molecule.
Dialogue: 0,0:08:31.89,0:08:33.53,Default,,0000,0000,0000,,So to me, this is\Npretty amazing.
Dialogue: 0,0:08:33.53,0:08:38.00,Default,,0000,0000,0000,,We actually are seeing how ATP\Nenergy can be used to-- we're
Dialogue: 0,0:08:38.00,0:08:47.57,Default,,0000,0000,0000,,going from chemical energy\Nor bond energy in ATP to
Dialogue: 0,0:08:47.57,0:08:48.82,Default,,0000,0000,0000,,mechanical energy.
Dialogue: 0,0:08:53.06,0:08:55.08,Default,,0000,0000,0000,,For me, that's amazing because\Nwhen I first learned about
Dialogue: 0,0:08:55.08,0:08:58.64,Default,,0000,0000,0000,,ATP-- people say, you use ATP to\Ndo everything in your cells
Dialogue: 0,0:08:58.64,0:08:59.65,Default,,0000,0000,0000,,and contract muscles.
Dialogue: 0,0:08:59.65,0:09:02.35,Default,,0000,0000,0000,,Well, gee, how do you go from\Nbond energy to actually
Dialogue: 0,0:09:02.35,0:09:04.85,Default,,0000,0000,0000,,contracting things, to actually\Ndoing what we see in
Dialogue: 0,0:09:04.85,0:09:07.01,Default,,0000,0000,0000,,our everyday world as\Nmechanical energy?
Dialogue: 0,0:09:07.01,0:09:09.39,Default,,0000,0000,0000,,And this is really where\Nit all occurs.
Dialogue: 0,0:09:09.39,0:09:12.14,Default,,0000,0000,0000,,This is really the core issue\Nthat's going on here.
Dialogue: 0,0:09:12.14,0:09:14.11,Default,,0000,0000,0000,,And you have to say, well, gee,\Nhow this thing change
Dialogue: 0,0:09:14.11,0:09:15.29,Default,,0000,0000,0000,,shape and all that?
Dialogue: 0,0:09:15.29,0:09:17.32,Default,,0000,0000,0000,,And you have to remember,\Nthese proteins, based on
Dialogue: 0,0:09:17.32,0:09:19.24,Default,,0000,0000,0000,,what's bonded to it and\Nwhat's not bonded to
Dialogue: 0,0:09:19.24,0:09:20.26,Default,,0000,0000,0000,,it, they change shape.
Dialogue: 0,0:09:20.26,0:09:23.81,Default,,0000,0000,0000,,And some of those shapes take\Nmore energy to attain, and
Dialogue: 0,0:09:23.81,0:09:26.61,Default,,0000,0000,0000,,then if you do the right things,\Nthat energy can be
Dialogue: 0,0:09:26.61,0:09:29.44,Default,,0000,0000,0000,,released and then it can\Npush another protein.
Dialogue: 0,0:09:29.44,0:09:30.92,Default,,0000,0000,0000,,But I find this just\Nfascinating.
Dialogue: 0,0:09:30.92,0:09:34.10,Default,,0000,0000,0000,,And now we can build up from\Nthis actin and myosin
Dialogue: 0,0:09:34.10,0:09:37.93,Default,,0000,0000,0000,,interactions to understand how\Nmuscles actually work.