1 00:00:07,400 --> 00:00:08,650 PROFESSOR: Good morning. 2 00:00:10,590 --> 00:00:12,270 Come on down. 3 00:00:12,270 --> 00:00:12,700 All right. 4 00:00:12,700 --> 00:00:20,170 So last time, we talked about the first couple of steps of 5 00:00:20,170 --> 00:00:23,570 the central dogma. 6 00:00:23,570 --> 00:00:33,200 The central dogma is this name given to the statement DNA 7 00:00:33,200 --> 00:00:35,260 goes to DNA by replication. 8 00:00:40,320 --> 00:00:46,016 DNA goes to RNA by the process of transcription. 9 00:00:50,090 --> 00:00:52,440 We call it transcription because it's such a direct 10 00:00:52,440 --> 00:00:56,020 copying of letter to letter. 11 00:00:56,020 --> 00:01:01,300 RNA goes to protein by a process of translation, 12 00:01:01,300 --> 00:01:05,340 because translation is the kind of word we would use 13 00:01:05,340 --> 00:01:06,650 between two different languages. 14 00:01:06,650 --> 00:01:07,850 And there are two different languages-- 15 00:01:07,850 --> 00:01:09,890 the languages of nucleotides and the 16 00:01:09,890 --> 00:01:12,880 language of amino acids. 17 00:01:12,880 --> 00:01:16,360 For what it's worth, it's name, the central dogma, goes 18 00:01:16,360 --> 00:01:20,980 back to Francis Crick, who called this the central dogma. 19 00:01:20,980 --> 00:01:23,700 He did it in a kind of a light-hearted way, although 20 00:01:23,700 --> 00:01:26,510 others since then have criticized it, saying, oh, 21 00:01:26,510 --> 00:01:28,190 this is dogmatic. 22 00:01:28,190 --> 00:01:31,740 Actually, Crick said not that DNA goes to 23 00:01:31,740 --> 00:01:32,670 RNA goes to the protein. 24 00:01:32,670 --> 00:01:36,190 He says that all information flows from nucleic acids to 25 00:01:36,190 --> 00:01:38,330 proteins and not back again. 26 00:01:38,330 --> 00:01:40,750 Because even then, Crick knew that in theory, there was no 27 00:01:40,750 --> 00:01:43,740 reason you couldn't go back from RNA to DNA, and as we'll 28 00:01:43,740 --> 00:01:45,410 see today, that happens. 29 00:01:45,410 --> 00:01:50,080 So sometimes people say, oh, well, the central dogma was 30 00:01:50,080 --> 00:01:52,480 proved wrong because RNA can go back to DNA. 31 00:01:52,480 --> 00:01:54,730 Well, actually, that was even anticipated right then at the 32 00:01:54,730 --> 00:01:56,645 very beginning, when they realized RNA and DNA were 33 00:01:56,645 --> 00:01:58,440 essentially equivalent information. 34 00:01:58,440 --> 00:02:03,900 The key step of converting nucleic acid information into 35 00:02:03,900 --> 00:02:07,150 protein information is translation. 36 00:02:07,150 --> 00:02:09,320 And that's the last bit we have to fill in 37 00:02:09,320 --> 00:02:11,050 and talk about today. 38 00:02:11,050 --> 00:02:14,970 So let me start by just reminding you-- because most 39 00:02:14,970 --> 00:02:16,760 of you know it-- 40 00:02:16,760 --> 00:02:19,600 how translation works. 41 00:02:19,600 --> 00:02:25,320 So, in translation, you have a particular RNA that has been 42 00:02:25,320 --> 00:02:28,860 made by the cell. 43 00:02:28,860 --> 00:02:30,460 Here's my RNA. 44 00:02:30,460 --> 00:02:33,540 It goes five prime to three prime. 45 00:02:33,540 --> 00:02:35,790 That's always the way we write these things. 46 00:02:35,790 --> 00:02:37,210 And it has some particular sequence. 47 00:02:37,210 --> 00:02:38,810 I'll make up a sequence here. 48 00:02:38,810 --> 00:02:52,110 A, U, A, C, G, A, U, G, A, A, G, A, G, G, C, C, C, dot dot 49 00:02:52,110 --> 00:02:57,270 dot dot dot, U, A, G, dot dot dot dot, three prime. 50 00:02:57,270 --> 00:02:59,140 All right. 51 00:02:59,140 --> 00:03:04,920 Somehow, that's going to be translated into a protein. 52 00:03:04,920 --> 00:03:09,310 It's translated according to a fantastic look-up up table. 53 00:03:09,310 --> 00:03:13,750 This look-up table is called the genetic code. 54 00:03:13,750 --> 00:03:15,390 And the rule, the algorithm-- 55 00:03:15,390 --> 00:03:18,260 and it's a fairly simple algorithm, well, nothing's 56 00:03:18,260 --> 00:03:21,940 ever really simple in biology, but it's close to simple-- 57 00:03:21,940 --> 00:03:24,740 is you run along the sequence from the beginning. 58 00:03:24,740 --> 00:03:25,820 And you guys could write this. 59 00:03:25,820 --> 00:03:28,200 Anybody who's taken basic computer programming. 60 00:03:28,200 --> 00:03:34,030 Run along the sequence and find the first occurrence of 61 00:03:34,030 --> 00:03:39,410 A, U, G. Why A, U, G? 62 00:03:39,410 --> 00:03:43,460 Because A, U, G is the place you start. 63 00:03:43,460 --> 00:03:46,680 That's how life worked it out, and that's what it does. 64 00:03:46,680 --> 00:03:53,120 After that, you parse the sequence in triplets. 65 00:03:53,120 --> 00:03:58,665 These triplets get the name codons. 66 00:04:02,350 --> 00:04:07,410 And then you keep going until you hit one of 67 00:04:07,410 --> 00:04:09,490 three possible triplets. 68 00:04:09,490 --> 00:04:16,560 U, A, G. U, A, A. U, G, A. And you stop there. 69 00:04:19,930 --> 00:04:23,350 Any MIT student should be able to write an algorithm that 70 00:04:23,350 --> 00:04:27,150 takes a string, finds the first occurrence of U, A, G, 71 00:04:27,150 --> 00:04:30,000 breaks it up into triplets passed there, keeps going 72 00:04:30,000 --> 00:04:34,010 until you encounter one of these three triplets. 73 00:04:34,010 --> 00:04:36,620 What do you do for a given triplet? 74 00:04:36,620 --> 00:04:38,660 You look it up against the table. 75 00:04:38,660 --> 00:04:40,610 How many triplets are there? 76 00:04:40,610 --> 00:04:44,550 How many three-letter words are there with the four 77 00:04:44,550 --> 00:04:47,128 nucleotides? 78 00:04:47,128 --> 00:04:47,570 AUDIENCE: 64. 79 00:04:47,570 --> 00:04:48,390 PROFESSOR: It's 4 to the 3rd-- 80 00:04:48,390 --> 00:04:50,600 64 possible words. 81 00:04:50,600 --> 00:04:54,800 I've used up three of them to be stop, so there are 4 to the 82 00:04:54,800 --> 00:04:59,360 3rd possible codons. 83 00:04:59,360 --> 00:05:01,920 That's 64. 84 00:05:01,920 --> 00:05:03,340 Three stops. 85 00:05:03,340 --> 00:05:10,790 The other 61 possible codons specify an amino acid. 86 00:05:10,790 --> 00:05:10,890 That's it. 87 00:05:10,890 --> 00:05:13,300 There's a look-up table. 88 00:05:13,300 --> 00:05:14,670 The genetic code. 89 00:05:14,670 --> 00:05:17,430 How many amino acids are there? 90 00:05:17,430 --> 00:05:17,960 20. 91 00:05:17,960 --> 00:05:21,560 And there are 61 possible codons, so that implies there 92 00:05:21,560 --> 00:05:23,780 is some redundancy. 93 00:05:23,780 --> 00:05:26,000 Some codons-- 94 00:05:26,000 --> 00:05:30,564 some amino acids are coded for by the same codon. 95 00:05:30,564 --> 00:05:31,330 Okay. 96 00:05:31,330 --> 00:05:32,200 That's fine. 97 00:05:32,200 --> 00:05:35,300 And in your book is the genetic code that is the 98 00:05:35,300 --> 00:05:36,920 look-up table here. 99 00:05:36,920 --> 00:05:52,070 The genetic code translates these codons into amino acids. 100 00:05:52,070 --> 00:05:54,870 Or to stop, in the case of the three stop signals. 101 00:05:54,870 --> 00:05:58,760 So for example, this A, U, G at the front is always 102 00:05:58,760 --> 00:06:02,200 translated into methionine. 103 00:06:02,200 --> 00:06:03,560 Met. 104 00:06:03,560 --> 00:06:07,630 And if I've got it right, this should be a lysine. 105 00:06:07,630 --> 00:06:08,130 Here we go. 106 00:06:08,130 --> 00:06:14,830 Arginine, proline, et cetera-- you just look it up. 107 00:06:14,830 --> 00:06:15,580 That's it. 108 00:06:15,580 --> 00:06:18,290 That's the order in which you make the proteins. 109 00:06:18,290 --> 00:06:21,310 So you send off an order written in RNA, you send it 110 00:06:21,310 --> 00:06:23,630 off to the factory, the factory sends you back a 111 00:06:23,630 --> 00:06:26,660 protein that is methionine, lysine, arginine, proline, 112 00:06:26,660 --> 00:06:28,270 blah, blah, blah, blah, blah. 113 00:06:28,270 --> 00:06:30,760 That's it. 114 00:06:30,760 --> 00:06:36,720 This genetic code is essentially universal amongst 115 00:06:36,720 --> 00:06:37,970 all of life. 116 00:06:42,183 --> 00:06:43,900 That's pretty stunning. 117 00:06:43,900 --> 00:06:45,150 What does that tell you? 118 00:06:45,150 --> 00:06:48,250 The fact that all of life uses virtually the identical 119 00:06:48,250 --> 00:06:49,100 genetic code? 120 00:06:49,100 --> 00:06:51,805 There's actually a tiny difference between prokaryotes 121 00:06:51,805 --> 00:06:55,130 and eukaryotes affecting a codon and there's a tiny 122 00:06:55,130 --> 00:06:56,290 difference somewhere else. 123 00:06:56,290 --> 00:06:59,560 But essentially, it's the exact same genetic code that 124 00:06:59,560 --> 00:07:01,630 all of life uses. 125 00:07:01,630 --> 00:07:04,220 It's very unlikely that this genetic code is the only 126 00:07:04,220 --> 00:07:07,990 possible way you could make a genetic code, right? 127 00:07:07,990 --> 00:07:11,410 So the fact that all of life uses, essentially, exactly the 128 00:07:11,410 --> 00:07:15,450 same code is pretty strong evidence that all currently 129 00:07:15,450 --> 00:07:19,960 existing life descends from a common ancestor. 130 00:07:19,960 --> 00:07:23,540 Because if these were evolved independently, it's extremely 131 00:07:23,540 --> 00:07:26,080 unlikely that you would have gotten exactly the same 132 00:07:26,080 --> 00:07:27,560 genetic code. 133 00:07:27,560 --> 00:07:29,880 So that's an interesting point that you can see from just the 134 00:07:29,880 --> 00:07:32,270 fact that everybody uses essentially the 135 00:07:32,270 --> 00:07:34,450 same genetic code. 136 00:07:34,450 --> 00:07:38,040 It's a universal genetic code. 137 00:07:38,040 --> 00:07:39,540 All right. 138 00:07:39,540 --> 00:07:45,160 So I've expressed this to you in a completely computer 139 00:07:45,160 --> 00:07:47,450 sciencey kind of way. 140 00:07:47,450 --> 00:07:50,960 But, of course, the cell doesn't do this by computer 141 00:07:50,960 --> 00:07:54,840 science because cells are unable to write C code. 142 00:07:54,840 --> 00:07:57,520 The reason that cells are unable to write C code is C 143 00:07:57,520 --> 00:08:01,710 wasn't really developed until the last several decades, and 144 00:08:01,710 --> 00:08:06,020 cells, pretty sure, precede the development of C code by 145 00:08:06,020 --> 00:08:06,900 Kernighan and Ritchie. 146 00:08:06,900 --> 00:08:10,980 So it's got to be the case that it's done some other way. 147 00:08:10,980 --> 00:08:12,620 How is it done? 148 00:08:12,620 --> 00:08:15,880 Well, it's done like this. 149 00:08:15,880 --> 00:08:17,750 And I'll just be very schematic and you'll 150 00:08:17,750 --> 00:08:19,150 get it in your book. 151 00:08:19,150 --> 00:08:20,400 There's a big machine. 152 00:08:22,750 --> 00:08:26,230 The big machine here is called the ribosome. 153 00:08:31,590 --> 00:08:35,860 It consists, itself, of proteins and RNAs, and it's a 154 00:08:35,860 --> 00:08:38,289 huge structure. 155 00:08:38,289 --> 00:08:42,230 The huge structure needs to read codons. 156 00:08:45,000 --> 00:08:46,720 And this is a case where Francis Crick 157 00:08:46,720 --> 00:08:48,500 drove everybody nuts. 158 00:08:48,500 --> 00:08:53,230 Francis Crick, back in the 1950s, just sat at his desk 159 00:08:53,230 --> 00:08:53,750 and thought. 160 00:08:53,750 --> 00:08:55,630 He was terrible at doing experiments-- 161 00:08:55,630 --> 00:08:57,420 nobody really wanted to let him do experiments. 162 00:08:57,420 --> 00:08:59,830 Francis was a great thinker. 163 00:08:59,830 --> 00:09:00,310 He thought. 164 00:09:00,310 --> 00:09:05,210 He said, golly, how can this sequence be translated into 165 00:09:05,210 --> 00:09:06,560 amino acids? 166 00:09:06,560 --> 00:09:08,880 Well, people at the time had all sorts of nutty ideas. 167 00:09:08,880 --> 00:09:11,440 Some of the nutty ideas was that the sequence of the RNA 168 00:09:11,440 --> 00:09:14,840 folded up into pockets that just fit a proline. 169 00:09:14,840 --> 00:09:17,710 And another pocket that just an arginine. 170 00:09:17,710 --> 00:09:20,040 And if you just think about the constraints to get that to 171 00:09:20,040 --> 00:09:21,510 work, it's nuts. 172 00:09:21,510 --> 00:09:24,840 That the sequence itself would form perfect binding pockets 173 00:09:24,840 --> 00:09:27,110 for the necessary amino acids. 174 00:09:27,110 --> 00:09:29,360 Crick said impossible. 175 00:09:29,360 --> 00:09:32,350 He said the really sensible way to do this, if I were 176 00:09:32,350 --> 00:09:35,100 running life, what I would do is I would 177 00:09:35,100 --> 00:09:37,510 have an adapter molecule. 178 00:09:37,510 --> 00:09:41,340 The adapter molecule would be some kind of a nucleic acid, 179 00:09:41,340 --> 00:09:45,960 and the nucleic acid would kind of match the codon on one 180 00:09:45,960 --> 00:09:52,020 end and have the amino acid on the other end. 181 00:09:52,020 --> 00:09:56,410 And then there'd be another adapter, and the adapter would 182 00:09:56,410 --> 00:09:59,640 have the next amino acid. 183 00:09:59,640 --> 00:10:03,840 And then you would catalyze a bond between them. 184 00:10:03,840 --> 00:10:07,360 Therefore, I predict, says Francis, there will be small 185 00:10:07,360 --> 00:10:11,420 adapter molecules, probably made out of RNAs themselves. 186 00:10:11,420 --> 00:10:14,145 And Francis called this the Adapter Hypothesis. 187 00:10:14,145 --> 00:10:17,160 It drove people crazy because, of course, he was right. 188 00:10:17,160 --> 00:10:21,590 People found the adapters and they would use transfer things 189 00:10:21,590 --> 00:10:23,360 that transfer information-- 190 00:10:23,360 --> 00:10:24,680 get called transfer RNAs. 191 00:10:33,880 --> 00:10:39,120 What happens is the ribosome has pockets in which these 192 00:10:39,120 --> 00:10:44,670 transfer RNAs basically come in, match their sequence, 193 00:10:44,670 --> 00:10:49,050 there's a codon each of these transfer RNAs has a matching 194 00:10:49,050 --> 00:10:52,060 anticodon that matches the triplet, and it has already 195 00:10:52,060 --> 00:10:54,380 attached to it an amino acid-- 196 00:10:54,380 --> 00:10:57,640 the right amino acid for that anticodon. 197 00:10:57,640 --> 00:10:59,340 How does that right amino acid get attached 198 00:10:59,340 --> 00:11:00,590 to the right tRNA? 199 00:11:04,970 --> 00:11:07,030 There's an enzyme. 200 00:11:07,030 --> 00:11:09,740 The job of that enzyme is to attach this amino acid, 201 00:11:09,740 --> 00:11:13,200 proline, to this transfer RNA. 202 00:11:13,200 --> 00:11:16,870 It's a Prolyl-tRNA synthetase. 203 00:11:16,870 --> 00:11:19,900 And its job is to put proline on the right tRNAs. 204 00:11:19,900 --> 00:11:22,760 There's another one that puts arginine on the right tRNAs. 205 00:11:22,760 --> 00:11:25,030 There's a whole business that's set up to get the right 206 00:11:25,030 --> 00:11:27,920 tRNAs, have the right amino acids attached to them through 207 00:11:27,920 --> 00:11:30,220 a bunch of enzymes floating around. 208 00:11:30,220 --> 00:11:34,332 So then these tRNAs with the amino acid attached drop in, 209 00:11:34,332 --> 00:11:37,910 they drop into the next position, and a bond-- 210 00:11:37,910 --> 00:11:41,410 the peptide bond-- is catalyzed. 211 00:11:41,410 --> 00:11:42,660 Interesting factoid. 212 00:11:45,730 --> 00:11:50,010 The catalysis, this enzymatic catalysis to join together 213 00:11:50,010 --> 00:11:53,020 those amino acids is actually carried out not by the 214 00:11:53,020 --> 00:11:55,900 proteins in a ribosome, but actually 215 00:11:55,900 --> 00:11:57,860 by RNA in the ribosome. 216 00:11:57,860 --> 00:12:01,122 The RNA is the enzyme. 217 00:12:01,122 --> 00:12:02,810 You know why that's kind of cool? 218 00:12:05,370 --> 00:12:08,050 If this bothers you, just forget it, but one of the 219 00:12:08,050 --> 00:12:10,720 mysteries about how you ever go from DNA to RNA to protein 220 00:12:10,720 --> 00:12:13,570 and all of that is how the whole thing ever got started. 221 00:12:13,570 --> 00:12:15,930 How could you possibly have gotten protein synthesis 222 00:12:15,930 --> 00:12:19,980 started if the things that were needed to make protein 223 00:12:19,980 --> 00:12:21,230 synthesis were proteins? 224 00:12:24,200 --> 00:12:28,720 So this is actually an echo of an ancient world 3 billion 225 00:12:28,720 --> 00:12:33,720 years ago, where this was all probably carried out by RNAs. 226 00:12:33,720 --> 00:12:37,480 RNA was probably the early catalysts for most things, and 227 00:12:37,480 --> 00:12:40,700 we still see evidence of the fact that even today your 228 00:12:40,700 --> 00:12:44,110 peptide bonds are catalyzed actually by RNA and they're 229 00:12:44,110 --> 00:12:46,260 doing the enzymatic work. 230 00:12:46,260 --> 00:12:47,630 Anyway, it's kind of cool. 231 00:12:47,630 --> 00:12:49,230 If you didn't get that, don't worry about it, but 232 00:12:49,230 --> 00:12:50,120 it's kind of cool. 233 00:12:50,120 --> 00:12:51,410 So then what happens after you attach the 234 00:12:51,410 --> 00:12:52,840 first two amino acids? 235 00:12:52,840 --> 00:12:57,320 Well, the ribosome chugs down here and grabs the next code-- 236 00:12:57,320 --> 00:12:58,320 these two shift over. 237 00:12:58,320 --> 00:13:00,210 You can either think about the ribosome moving this way or 238 00:13:00,210 --> 00:13:01,680 the RNA moving that way. 239 00:13:01,680 --> 00:13:04,830 The next tRNA drops in, the next bond gets made, chugs 240 00:13:04,830 --> 00:13:07,920 over, the next one drops in, the next one gets made, and 241 00:13:07,920 --> 00:13:10,860 onward like that until it hits a stop codon at which, it 242 00:13:10,860 --> 00:13:12,830 releases it. 243 00:13:12,830 --> 00:13:14,260 The ribosome knows to release it. 244 00:13:14,260 --> 00:13:15,900 There's actually a little factor that drops in and tells 245 00:13:15,900 --> 00:13:17,120 it to release it there. 246 00:13:17,120 --> 00:13:18,800 And that's how you make proteins-- 247 00:13:18,800 --> 00:13:19,730 kind of cool. 248 00:13:19,730 --> 00:13:21,345 It works very well. 249 00:13:21,345 --> 00:13:23,200 It chugs along in that fashion. 250 00:13:23,200 --> 00:13:26,560 For you computer scientists, what you basically have is a 251 00:13:26,560 --> 00:13:27,990 two-tape turing machine-- 252 00:13:27,990 --> 00:13:30,510 you're reading one tape and writing to the other tape. 253 00:13:30,510 --> 00:13:32,100 There's a nucleic acid tape and there's 254 00:13:32,100 --> 00:13:33,600 an amino acid tape. 255 00:13:33,600 --> 00:13:36,290 If you're not a computer scientist, forget I said that. 256 00:13:36,290 --> 00:13:37,080 OK. 257 00:13:37,080 --> 00:13:41,420 So it's basically a two-tape tape turing machine where the 258 00:13:41,420 --> 00:13:45,370 RNA is coming through here and the protein is coming out that 259 00:13:45,370 --> 00:13:48,310 way, but the amino acids attach to each other 260 00:13:48,310 --> 00:13:51,220 until it comes off. 261 00:13:51,220 --> 00:13:54,110 In fact, actually, very recently, a Nobel Prize was 262 00:13:54,110 --> 00:13:57,770 awarded last year for beautiful, beautiful work on 263 00:13:57,770 --> 00:14:01,030 how this actually takes place-- the molecular details 264 00:14:01,030 --> 00:14:02,780 of the ribosome. 265 00:14:02,780 --> 00:14:04,600 Really gorgeous. 266 00:14:04,600 --> 00:14:07,694 Any questions about that? 267 00:14:07,694 --> 00:14:09,152 Yeah. 268 00:14:09,152 --> 00:14:10,610 AUDIENCE: Is that not susceptible to the same error 269 00:14:10,610 --> 00:14:12,560 as replication is? 270 00:14:12,560 --> 00:14:15,260 PROFESSOR: Oh, is that not susceptible to the same error? 271 00:14:18,250 --> 00:14:19,870 Does the ribosome ever make mistakes? 272 00:14:22,500 --> 00:14:24,740 It does. 273 00:14:24,740 --> 00:14:28,342 What happens if you make the wrong protein? 274 00:14:28,342 --> 00:14:30,140 AUDIENCE: [INAUDIBLE]. 275 00:14:30,140 --> 00:14:31,440 PROFESSOR: Oh well. 276 00:14:31,440 --> 00:14:34,890 The answer turns out to be "oh well" because for any given 277 00:14:34,890 --> 00:14:37,180 DNA, you make lots of RNAs. 278 00:14:37,180 --> 00:14:39,335 For any RNA, you use it again and again to 279 00:14:39,335 --> 00:14:40,810 make lots of proteins. 280 00:14:40,810 --> 00:14:43,670 And if the occasional protein is not so good, if the quality 281 00:14:43,670 --> 00:14:47,660 control is not perfect, it's much less serious than if your 282 00:14:47,660 --> 00:14:50,820 master instructions in the DNA were not perfect. 283 00:14:50,820 --> 00:14:52,550 So the cell actually devotes a lot less 284 00:14:52,550 --> 00:14:54,360 attention to quality control. 285 00:14:54,360 --> 00:14:54,550 Now. 286 00:14:54,550 --> 00:14:56,570 That's not to say there isn't important quality control. 287 00:14:56,570 --> 00:14:58,850 There are quality control mechanisms, but it doesn't 288 00:14:58,850 --> 00:15:01,840 have to be as accurate as one error in a billion, like you 289 00:15:01,840 --> 00:15:03,810 want to be in copying your DNA. 290 00:15:03,810 --> 00:15:06,910 And that's really an important point, is the archival copy 291 00:15:06,910 --> 00:15:10,580 has to be really good, but little yellow sticky notes-- 292 00:15:10,580 --> 00:15:12,520 what you make from it, which are basically RNA or the 293 00:15:12,520 --> 00:15:14,810 little yellow sticky notes you copied down-- they don't have 294 00:15:14,810 --> 00:15:15,430 to be perfect. 295 00:15:15,430 --> 00:15:17,330 And each copy, the protein doesn't have to be-- 296 00:15:17,330 --> 00:15:19,750 and if the protein is not perfect, there are mechanisms 297 00:15:19,750 --> 00:15:22,540 that take unfolded proteins and degrade them. 298 00:15:22,540 --> 00:15:26,040 So it turns out there are ways to achieve quality control in 299 00:15:26,040 --> 00:15:26,610 that sense. 300 00:15:26,610 --> 00:15:27,860 It's a great question.