>So, let's say instead these adaptors recognize 2 amino acids at a time >(still probably not robust enough). Then, one would need 2^20 >adaptors, already a far greater number of gene products than that >present in any genome than I know of...
Surely only 20^2, which is 400? A lot, but managable. James -- Dr. James W. Murray David Phillips Research Fellow Division on Molecular Biosciences Imperial College, LONDON Tel: +44 (0)20 759 48895 ________________________________________ From: CCP4 bulletin board [ccp...@jiscmail.ac.uk] On Behalf Of Greg Alushin [galus...@berkeley.edu] Sent: Tuesday, September 07, 2010 3:19 AM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Reverse Translatase Hi Jacob- What an intriguing proposition. I can think of multiple reasons why such a system would not exist, but there is a mechanistic one which is most fundamental, having to do with the nature of the genetic code. Say that there is a cellular machine which would unfold a protein and expose it to some sort of reading system (already a hard problem). There is now the issue of transforming the amino acid information into nucleic acid information. For simplicity let's assume that this system only uses one codon per amino acid, bypassing the degeneracy problem. How would the cell then read off the amino acid sequence? It seems the simplest solution would be analogous to translation, i.e. having adaptor molecules analogues to tRNAs which would guide an enzyme that synthesized the nucleic acid. Otherwise, one would have to invoke the idea of a single enzyme recognizing every amino acid, which seems impossible to me. As we know, the problem of protein-protein recognition is relatively complex. At a minimum, one would need 20 adaptor proteins to recognize the 20 canonical amino acids: however, it seems unlikely that recognition of a single amino acid would be robust enough to select for the correct adaptor molecule. So, let's say instead these adaptors recognize 2 amino acids at a time (still probably not robust enough). Then, one would need 2^20 adaptors, already a far greater number of gene products than that present in any genome than I know of... It might be tempting to draw an analogy between this system and the immune system, where an incredible diversity is generated from a small number of genes. However, diverse immune proteins all take the same input sequence (say antigen recognition) and lead to a single response, whereas this system has a 1 to 1 correspondence between inputs (protein sequence) and outputs (nucleic acid sequences), and thus there is no way that a randomization system could generate the required diversity. Cheers, -Greg Alushin Nogales lab UC Berkeley On Sep 6, 2010, at 7:12 PM, Michael Thompson wrote: > Jacob, > > The idea is enticing, but don't forget that there are multiple > degenerate codons for a given amino acid. Once the protein is > synthesized, the specific codon information is lost. > > I think that's a fundamental problem. > > Keep the ideas coming, > > Mike Thompson > > > > > ----- Original Message ----- > From: "Jacob Keller" <j-kell...@fsm.northwestern.edu> > To: CCP4BB@JISCMAIL.AC.UK > Sent: Monday, September 6, 2010 6:36:14 PM GMT -08:00 US/Canada > Pacific > Subject: [ccp4bb] Reverse Translatase > > Dear Crystallographers, > > does anyone know of any conceptual reason why a reverse translatase > enzyme > (protein-->nucleic acid) could not exist? I can think of so many > things for > which such an enzyme would be helpful, both to cells and to > scientists...! > Unless there is something I am missing, it would seem to me > conceptually > almost impossible that it *not* exist. > > Best Regards, > > Jacob Keller > > > ******************************************* > Jacob Pearson Keller > Northwestern University > Medical Scientist Training Program > Dallos Laboratory > F. Searle 1-240 > 2240 Campus Drive > Evanston IL 60208 > lab: 847.491.2438 > cel: 773.608.9185 > email: j-kell...@northwestern.edu > ******************************************* > > -- > Michael C. Thompson > > Graduate Student > > Biochemistry & Molecular Biology Division > > Department of Chemistry & Biochemistry > > University of California, Los Angeles > > mi...@chem.ucla.edu
