All language subtitles for Amazing proteins secondary strucrue 15

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Would you like to inspect the original subtitles? These are the user uploaded subtitles that are being translated: 0 00:00:00,355 --> 00:00:06,430 ERIC S. LANDER: It turns out that one incredibly smart guy, one extremely 1 00:00:06,430 --> 00:00:11,390 smart guy, said, I don't want to think about the complications. 2 00:00:11,390 --> 00:00:13,980 I want to think about the simple bits. 3 00:00:13,980 --> 00:00:16,320 Let's think about the simple bits first. 4 00:00:16,320 --> 00:00:27,740 And so proteins, secondary structure. 5 00:00:27,740 --> 00:00:32,210 He said, I'm not going to solve the whole thing. 6 00:00:32,210 --> 00:00:36,580 But are there any simple rules? 7 00:00:36,580 --> 00:00:41,880 Now this guy was one of the world's best ever, history's best ever 8 00:00:41,880 --> 00:00:44,910 chemists, a guy called Linus Pauling. 9 00:00:44,910 --> 00:00:49,190 Linus Pauling, who some of you may know, amongst other things, he won two 10 00:00:49,190 --> 00:00:54,480 Nobel prizes, one in chemistry and one for peace. 11 00:00:54,480 --> 00:00:57,914 It's interesting, worth looking up Linus Pauling. 12 00:00:57,914 --> 00:01:03,150 Linus Pauling, he was a very intuitive chemist. 13 00:01:03,150 --> 00:01:09,870 In 1948, he was the Eastman professor at Oxford University in England. 14 00:01:09,870 --> 00:01:12,490 And he caught a cold. 15 00:01:12,490 --> 00:01:15,130 And the weather is terrible, often, in England. 16 00:01:15,130 --> 00:01:17,260 I spent three years going to graduate school in England. 17 00:01:17,260 --> 00:01:19,480 And the weather can be pretty bad. 18 00:01:19,480 --> 00:01:21,120 Linus caught a cold. 19 00:01:21,120 --> 00:01:23,590 And Linus was laid up in bed. 20 00:01:23,590 --> 00:01:26,290 And what most people might do, you know, laid up in bed was 21 00:01:26,290 --> 00:01:27,670 not what Linus did. 22 00:01:27,670 --> 00:01:29,520 Linus said, Oh, I'm laid up in bed. 23 00:01:29,520 --> 00:01:31,010 I can't go to the lab. 24 00:01:31,010 --> 00:01:33,700 I'm going to figure out how proteins fold. 25 00:01:33,700 --> 00:01:35,220 [LAUGHTER] 26 00:01:35,220 --> 00:01:39,590 ERIC S. LANDER: And he had at his disposal paper. 27 00:01:39,590 --> 00:01:42,230 And he started doing origami. 28 00:01:42,230 --> 00:01:46,900 He started folding the paper along the ways that the various different-- like 29 00:01:46,900 --> 00:01:48,230 those bonds, I could tell you-- 30 00:01:48,230 --> 00:01:50,650 those rotating thises and thats. 31 00:01:50,650 --> 00:01:54,290 He said, can I make any regularities out of this? 32 00:01:54,290 --> 00:01:56,520 And, of course, what he said was, look, I've got a 33 00:01:56,520 --> 00:01:58,060 peptide bond here, right? 34 00:01:58,060 --> 00:01:58,340 Let's see. 35 00:01:58,340 --> 00:02:00,870 I'm just going to jump right into the middle of a protein here. 36 00:02:00,870 --> 00:02:21,330 C, I've got my C alpha, I've got C alpha, C alpha. 37 00:02:26,510 --> 00:02:31,340 He said, I know those side chains are very, very important. 38 00:02:31,340 --> 00:02:33,480 But I'm going to totally forget about them. 39 00:02:33,480 --> 00:02:35,320 I'm not going to care about the side chain. 40 00:02:35,320 --> 00:02:36,940 I'm not going to care about the side chain. 41 00:02:36,940 --> 00:02:38,300 I'm not going to care about the side chain. 42 00:02:38,300 --> 00:02:47,290 I'm going to note that I have all this wonderful hydrogen bonding potential. 43 00:02:47,290 --> 00:02:51,210 I've got those bonds along the backbone of the protein that can make 44 00:02:51,210 --> 00:02:52,730 hydrogen bonds. 45 00:02:52,730 --> 00:02:55,790 So let me utterly ignore the side chains. 46 00:02:55,790 --> 00:03:02,860 And let me ask, with my paper origami, what patterns can I make making 47 00:03:02,860 --> 00:03:08,550 hydrogen bonds of just the peptide of the protein chain here? 48 00:03:08,550 --> 00:03:16,970 And I will not do justice to it, but what he did was he said, you could 49 00:03:16,970 --> 00:03:21,370 kind of make a helical structure. 50 00:03:21,370 --> 00:03:33,520 And in that helical structure, you could have this pointing at this. 51 00:03:33,520 --> 00:03:37,540 I could have my carboxyl and my amino pointing at each other. 52 00:03:37,540 --> 00:03:43,740 And, he said, if I fold my origami just the right way, it can go around 53 00:03:43,740 --> 00:03:52,050 and around and around, such that at every place it's able to 54 00:03:52,050 --> 00:03:55,470 make bonds like that. 55 00:03:55,470 --> 00:03:59,630 And it's able to continue to come down and make bonds, and make bonds. 56 00:03:59,630 --> 00:04:03,750 And you could get a whole bunch of hydrogen bonds from that backbone 57 00:04:03,750 --> 00:04:04,960 going around. 58 00:04:04,960 --> 00:04:06,290 And you get a helix. 59 00:04:06,290 --> 00:04:18,720 And that helix has 3.7 amino acids per turn, per turn of the helix, by just 60 00:04:18,720 --> 00:04:24,680 perfectly lining up the hydrogen bonds that you can have between this 61 00:04:24,680 --> 00:04:29,460 carboxyl and then 3.7 later, this amino. 62 00:04:29,460 --> 00:04:32,360 And then, onward and onward and onward, every one of them making this 63 00:04:32,360 --> 00:04:36,610 beautiful bond, and making these beautiful hydrogen bonds. 64 00:04:36,610 --> 00:04:38,880 This was the sort of thing that pissed people off. 65 00:04:38,880 --> 00:04:44,010 Because Linus Pauling, sitting in bed with the flu, is able to come up with 66 00:04:44,010 --> 00:04:48,740 the fundamentals of protein structure by just thinking about it. 67 00:04:48,740 --> 00:04:53,360 You know, this is amazing and did not necessarily endear him to others who 68 00:04:53,360 --> 00:04:54,870 didn't think of such things. 69 00:04:54,870 --> 00:04:58,730 Linus calls this the alpha helix. 70 00:05:03,450 --> 00:05:10,130 Not to be outdone, he also says, there's another way I could imagine 71 00:05:10,130 --> 00:05:14,020 using all this hydrogen bonding potential. 72 00:05:14,020 --> 00:05:16,860 Kinda suppose there was a chain of-- 73 00:05:16,860 --> 00:05:19,470 and I'm just going to draw this very roughly here-- 74 00:05:19,470 --> 00:05:23,160 somehow a chain like that. 75 00:05:23,160 --> 00:05:24,120 And I have-- 76 00:05:24,120 --> 00:05:28,470 so here's my peptide backbone here, my protein backbone's going along here-- 77 00:05:28,470 --> 00:05:43,680 and I could also do it like that and make lots and lots of bonds along a 78 00:05:43,680 --> 00:05:44,420 long chain. 79 00:05:44,420 --> 00:05:52,210 So instead of making a spiral, a helix, I could have two strands, one 80 00:05:52,210 --> 00:05:57,780 strand and another strand, and I could have lots of hydrogen bonds between 81 00:05:57,780 --> 00:06:00,370 the strands. 82 00:06:00,370 --> 00:06:06,060 And in fact, it turns out, you can get the strands going back, and the 83 00:06:06,060 --> 00:06:08,250 strands going back. 84 00:06:08,250 --> 00:06:12,352 And what you can make are beta sheets. 85 00:06:12,352 --> 00:06:14,260 He utterly ignores the amino acids. 86 00:06:14,260 --> 00:06:16,370 Now you know it's wrong to ignore these amino acids. 87 00:06:16,370 --> 00:06:18,200 I've just told you about these cool amino acids. 88 00:06:18,200 --> 00:06:22,010 But it turns out, Linus was kind of smart here. 89 00:06:22,010 --> 00:06:27,190 He said, many times the amino acids won't matter enough, and its 90 00:06:27,190 --> 00:06:30,830 permissive to be able to make an alpha helix. 91 00:06:30,830 --> 00:06:33,860 And some amino acids are pretty fine with being in an alpha helix. 92 00:06:33,860 --> 00:06:36,500 And some amino acids, you know, they're better for, 93 00:06:36,500 --> 00:06:37,840 you know, beta sheets. 94 00:06:37,840 --> 00:06:42,440 And then there's another possibility, which is neither of the above. 95 00:06:42,440 --> 00:06:46,440 Neither of the above is called loops. 96 00:06:49,770 --> 00:06:54,350 And it means stuff, things that aren't easily classified as beautiful 97 00:06:54,350 --> 00:06:57,400 helices, not easily classified as sheets, but kind of 98 00:06:57,400 --> 00:06:59,050 more random-y loops. 99 00:06:59,050 --> 00:07:04,065 And at a first order approximation, you can kind of make cartoons of a 100 00:07:04,065 --> 00:07:08,380 protein, a cartoon of a protein that has either alpha helices in parts of 101 00:07:08,380 --> 00:07:12,020 it, beta sheets in part of it, or loops in part of it. 102 00:07:12,020 --> 00:07:14,780 Let's actually take a look. 103 00:07:14,780 --> 00:07:18,160 Right here, here's our alpha helix. 104 00:07:18,160 --> 00:07:23,970 And the hydrogen bonds are holding it together along a certain length. 105 00:07:23,970 --> 00:07:28,320 Now, one of the amino acids that will not consent to be part of an alpha 106 00:07:28,320 --> 00:07:32,860 helix, is the one amino acid that's not an amino acid. 107 00:07:32,860 --> 00:07:38,140 Remember, I said that kinky thing, proline, has a constraint. 108 00:07:38,140 --> 00:07:43,290 When there's a proline in an alpha helix, it breaks that alpha helix. 109 00:07:43,290 --> 00:07:46,450 It's kinky, OK? 110 00:07:46,450 --> 00:07:48,230 Here's some beta sheet. 111 00:07:48,230 --> 00:07:51,730 We've got hydrogen bonds, hydrogen bonds, and you can get 112 00:07:51,730 --> 00:07:53,730 these marvelous sheets. 113 00:07:53,730 --> 00:07:56,460 Biologists draw this, and chemists draw this in all different ways. 114 00:07:56,460 --> 00:07:59,710 We have these things we tend to call ribbon diagrams. 115 00:07:59,710 --> 00:08:00,850 Here's my ribbon. 116 00:08:00,850 --> 00:08:02,810 And this long sheet here, we just draw it. 117 00:08:02,810 --> 00:08:04,780 And it's kind of a very nice beta sheet, and it's hydrogen 118 00:08:04,780 --> 00:08:05,800 bonding that way. 119 00:08:05,800 --> 00:08:06,680 So what's this part here? 120 00:08:06,680 --> 00:08:09,010 We call this random coil. 121 00:08:09,010 --> 00:08:10,130 They're all a little bit different. 122 00:08:10,130 --> 00:08:12,800 There's some random coil here and some random coil there. 123 00:08:12,800 --> 00:08:15,170 And so we see beta sheet structures. 124 00:08:15,170 --> 00:08:17,640 We see alpha helix structures. 125 00:08:17,640 --> 00:08:19,184 Any questions? 126 00:08:19,184 --> 00:08:19,950 All right. 127 00:08:19,950 --> 00:08:22,710 So this doesn't totally explain all protein folding, because we've got 128 00:08:22,710 --> 00:08:24,370 those amino acids to care about. 129 00:08:24,370 --> 00:08:27,540 But it gets us some very basic descriptions, alpha 130 00:08:27,540 --> 00:08:29,260 helices, beta sheets. 131 00:08:29,260 --> 00:08:31,730 Take a few minutes to think about what you've just heard by 132 00:08:31,730 --> 00:08:32,980 answering this question. 10809

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