Self-Organizing Bio-structures. NB2-2009 L.Duroux. Lecture 2. Macromolecular Sequences. Introduction-questions:. How do we move along from prebiotic small molecules to oligomers and polymers (DNA & proteins)? Why the need for long polymeric chains vs cooperation of small ones?
Examples of the ”necessity” for growing larger peptides
A common case of ”chain-growth”:
Protein structural domains
Active site (combination of ancestral active site residues)
Putative ancestral b-barrel structure
‘Modern’ 2-b-barrel structure
Activity 1000-10,000 times enhanced
A multiple-domain protein: pyruvate kinase
b barrel regulatory domain
a/b barrel catalytic substrate binding domain
a/b nucleotide binding domain
1 continuous + 2 discontinuous domains
A step towards macromolecules
rA = kAA / kAB and rB = kBB / kBA
bean bags, packing
Prebiotic activation of monomers
No explanation for NMPs
No explanation for the retention of particular sequences of nucleotides
The problem of peptide chains ”selection”
& never-born proteins...
Only folded peptides resist to thrombin cleavage
80 clones tested: 20% resistant
The problem of formation (and ”selection”) of macromolecular sequences
* Catalytic residue
= peptidase activity
specific to terminal
As a result of contingency:
pH, salinity, temperature...
And life could begin...?
Homochirality in chains& chain growth
The case of vinyl polymers : polypropylene (G. Natta)
Confers helical conformations to polymer in crystals
White: random distribution
Grey: observed composition
Prebioticchemistrycouldexplain formation of short peptidechains / oligonucleotides
Still problems withactivationchemistry
Never-born proteins universe is huge: some NBP can fold
Homochirality in chains is naturallyselected, canbeexplainedstatistically.