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Functional capabilities of the earliest peptides and the emergence of life.

Milner-White EJ, Russell MJ - Genes (Basel) (2011)

Bottom Line: Considering how biological macromolecules first evolved, probably within a marine environment, it seems likely the very earliest peptides were not encoded by nucleic acids, or at least not via the genetic code as we know it.An objective of the present work is to demonstrate that sequence-independent peptides, or peptides with variable and unreliable lengths and sequences, have the potential to perform a variety of chemically useful functions such as anion and cation binding and membrane and channel formation as well as simple types of catalysis.These functions tend to be performed with the assistance of the main chain CONH atoms rather than the more variable or limited side chain atoms of the peptides presumed to exist then.

View Article: PubMed Central - PubMed

Affiliation: College of Medical, Veterinary and Life Sciences, Glasgow University, Glasgow G128QQ, UK. J.Milner-White@bio.gla.ac.uk.

ABSTRACT
Considering how biological macromolecules first evolved, probably within a marine environment, it seems likely the very earliest peptides were not encoded by nucleic acids, or at least not via the genetic code as we know it. An objective of the present work is to demonstrate that sequence-independent peptides, or peptides with variable and unreliable lengths and sequences, have the potential to perform a variety of chemically useful functions such as anion and cation binding and membrane and channel formation as well as simple types of catalysis. These functions tend to be performed with the assistance of the main chain CONH atoms rather than the more variable or limited side chain atoms of the peptides presumed to exist then.

No MeSH data available.


Related in: MedlinePlus

Motif structures (a) nest binding a carbonyl oxygen. (b) nest binding a phosphate ion. (c) nest binding a Fe4S4 iron-sulfur center. (d) covalent Ni+-tetrapeptide complex—a peptide pigment. (e) two of the four peptides forming the selectivity filter of the potassium channel. (f) the peptide forming the aquaporin channel. (g) catgrip bound to a calcium ion. (h) niche3 bound to a K+ ion. (i) niche4 bound to a K+ ion. (j) vancomycin, which can be regarded as a nest designed to bind a carboxylate group in the bacterial cell wall (the carboxylate of acetate is seen in sticks and the antibiotic is in spacefill). (k) three strands of α-sheet. (note the similarity in conformation with e and f). α-sheet, unlike β-sheet, has an inherent polarity, indicated by the partial charges δ+ and δ−. In (a-i) and (k) the side chains are omitted. Colors: carbon, green; oxygen, red; nitrogen, blue; sulfur, mustard; potassium, purple; iron, rust; nickel, brown; chlorine, green; calcium, yellow; phosphorus, orange.
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f2-genes-02-00671: Motif structures (a) nest binding a carbonyl oxygen. (b) nest binding a phosphate ion. (c) nest binding a Fe4S4 iron-sulfur center. (d) covalent Ni+-tetrapeptide complex—a peptide pigment. (e) two of the four peptides forming the selectivity filter of the potassium channel. (f) the peptide forming the aquaporin channel. (g) catgrip bound to a calcium ion. (h) niche3 bound to a K+ ion. (i) niche4 bound to a K+ ion. (j) vancomycin, which can be regarded as a nest designed to bind a carboxylate group in the bacterial cell wall (the carboxylate of acetate is seen in sticks and the antibiotic is in spacefill). (k) three strands of α-sheet. (note the similarity in conformation with e and f). α-sheet, unlike β-sheet, has an inherent polarity, indicated by the partial charges δ+ and δ−. In (a-i) and (k) the side chains are omitted. Colors: carbon, green; oxygen, red; nitrogen, blue; sulfur, mustard; potassium, purple; iron, rust; nickel, brown; chlorine, green; calcium, yellow; phosphorus, orange.

Mentions: Some of the properties of these peptides, as will be shown, lend themselves to assisting the development of prebiotic systems in ways that are hard to envisage for polynucleotides. They continue offering low entropy sites though at a much smaller scale and therefore more effectively than do the mineral compartments. We note in passing that lipids too are difficult to synthesize under prebiotic conditions and have even less sequestering power than polynucleotides. Moreover, cogent arguments have been advanced that some protein features are the most ancient conserved macromolecular entities that exist [23-28]. Thus, we suggest that, once the mineral hatchery for life was built, the first major biomolecules produced there were peptides that took over the roles of the minerals as compartment walls, and chelated inorganic clusters as precursors of the metal and metal sulfide proteins as well as of the phosphates (Figure 2a) [29,30]. Moreover, a synergy would have existed between peptides on the one hand and metabolic entities on the other [31-33]. This idea does not preclude the existence of an RNA or protein/RNA world but the premise is that any such era came later and was probably derived from the coenzymes [14,34,35]. It seems improbable the earliest peptides consisted of large domains of tightly folded polypeptide chains as in present day proteins. Instead they would have been small, simple and heterochiral in nature. Without a genetic code as we know it, different polypeptide molecules probably had a variety of compositions and sequences and thus lacked defined large-scale three-dimensional structures. Although theoretically not limited to the 20 amino acids in current proteins, amino acid occurrence was governed by ease of synthesis, with a preponderance of glycines and a few others probably in the order alanine > aspartate > valine [6]. These others were almost certainly heterochiral at least initially [36]. The homochirality of present-day amino acids has a great effect on the structures they adopt [37] and the α-helix, especially, is only favored in homochiral peptides. The consequence is that early peptides were more exposed to solvent water and variable and motile in their 3D structure than present-day evolved proteins. This does not mean they lacked any structure at all, as, especially on the scale of a few Å, recurring features do occur. One aspect is that the variability and unpredictability of the side chains—their stochastic nature—would have caused main chain, rather than side chain, features to be employed for functional purposes. Most of the motifs described below are ones that only employ main chain atoms for various anion or cation binding activities and this aspect would have made them functionally useful during the emergence of metabolism and the onset of life.


Functional capabilities of the earliest peptides and the emergence of life.

Milner-White EJ, Russell MJ - Genes (Basel) (2011)

Motif structures (a) nest binding a carbonyl oxygen. (b) nest binding a phosphate ion. (c) nest binding a Fe4S4 iron-sulfur center. (d) covalent Ni+-tetrapeptide complex—a peptide pigment. (e) two of the four peptides forming the selectivity filter of the potassium channel. (f) the peptide forming the aquaporin channel. (g) catgrip bound to a calcium ion. (h) niche3 bound to a K+ ion. (i) niche4 bound to a K+ ion. (j) vancomycin, which can be regarded as a nest designed to bind a carboxylate group in the bacterial cell wall (the carboxylate of acetate is seen in sticks and the antibiotic is in spacefill). (k) three strands of α-sheet. (note the similarity in conformation with e and f). α-sheet, unlike β-sheet, has an inherent polarity, indicated by the partial charges δ+ and δ−. In (a-i) and (k) the side chains are omitted. Colors: carbon, green; oxygen, red; nitrogen, blue; sulfur, mustard; potassium, purple; iron, rust; nickel, brown; chlorine, green; calcium, yellow; phosphorus, orange.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3927598&req=5

f2-genes-02-00671: Motif structures (a) nest binding a carbonyl oxygen. (b) nest binding a phosphate ion. (c) nest binding a Fe4S4 iron-sulfur center. (d) covalent Ni+-tetrapeptide complex—a peptide pigment. (e) two of the four peptides forming the selectivity filter of the potassium channel. (f) the peptide forming the aquaporin channel. (g) catgrip bound to a calcium ion. (h) niche3 bound to a K+ ion. (i) niche4 bound to a K+ ion. (j) vancomycin, which can be regarded as a nest designed to bind a carboxylate group in the bacterial cell wall (the carboxylate of acetate is seen in sticks and the antibiotic is in spacefill). (k) three strands of α-sheet. (note the similarity in conformation with e and f). α-sheet, unlike β-sheet, has an inherent polarity, indicated by the partial charges δ+ and δ−. In (a-i) and (k) the side chains are omitted. Colors: carbon, green; oxygen, red; nitrogen, blue; sulfur, mustard; potassium, purple; iron, rust; nickel, brown; chlorine, green; calcium, yellow; phosphorus, orange.
Mentions: Some of the properties of these peptides, as will be shown, lend themselves to assisting the development of prebiotic systems in ways that are hard to envisage for polynucleotides. They continue offering low entropy sites though at a much smaller scale and therefore more effectively than do the mineral compartments. We note in passing that lipids too are difficult to synthesize under prebiotic conditions and have even less sequestering power than polynucleotides. Moreover, cogent arguments have been advanced that some protein features are the most ancient conserved macromolecular entities that exist [23-28]. Thus, we suggest that, once the mineral hatchery for life was built, the first major biomolecules produced there were peptides that took over the roles of the minerals as compartment walls, and chelated inorganic clusters as precursors of the metal and metal sulfide proteins as well as of the phosphates (Figure 2a) [29,30]. Moreover, a synergy would have existed between peptides on the one hand and metabolic entities on the other [31-33]. This idea does not preclude the existence of an RNA or protein/RNA world but the premise is that any such era came later and was probably derived from the coenzymes [14,34,35]. It seems improbable the earliest peptides consisted of large domains of tightly folded polypeptide chains as in present day proteins. Instead they would have been small, simple and heterochiral in nature. Without a genetic code as we know it, different polypeptide molecules probably had a variety of compositions and sequences and thus lacked defined large-scale three-dimensional structures. Although theoretically not limited to the 20 amino acids in current proteins, amino acid occurrence was governed by ease of synthesis, with a preponderance of glycines and a few others probably in the order alanine > aspartate > valine [6]. These others were almost certainly heterochiral at least initially [36]. The homochirality of present-day amino acids has a great effect on the structures they adopt [37] and the α-helix, especially, is only favored in homochiral peptides. The consequence is that early peptides were more exposed to solvent water and variable and motile in their 3D structure than present-day evolved proteins. This does not mean they lacked any structure at all, as, especially on the scale of a few Å, recurring features do occur. One aspect is that the variability and unpredictability of the side chains—their stochastic nature—would have caused main chain, rather than side chain, features to be employed for functional purposes. Most of the motifs described below are ones that only employ main chain atoms for various anion or cation binding activities and this aspect would have made them functionally useful during the emergence of metabolism and the onset of life.

Bottom Line: Considering how biological macromolecules first evolved, probably within a marine environment, it seems likely the very earliest peptides were not encoded by nucleic acids, or at least not via the genetic code as we know it.An objective of the present work is to demonstrate that sequence-independent peptides, or peptides with variable and unreliable lengths and sequences, have the potential to perform a variety of chemically useful functions such as anion and cation binding and membrane and channel formation as well as simple types of catalysis.These functions tend to be performed with the assistance of the main chain CONH atoms rather than the more variable or limited side chain atoms of the peptides presumed to exist then.

View Article: PubMed Central - PubMed

Affiliation: College of Medical, Veterinary and Life Sciences, Glasgow University, Glasgow G128QQ, UK. J.Milner-White@bio.gla.ac.uk.

ABSTRACT
Considering how biological macromolecules first evolved, probably within a marine environment, it seems likely the very earliest peptides were not encoded by nucleic acids, or at least not via the genetic code as we know it. An objective of the present work is to demonstrate that sequence-independent peptides, or peptides with variable and unreliable lengths and sequences, have the potential to perform a variety of chemically useful functions such as anion and cation binding and membrane and channel formation as well as simple types of catalysis. These functions tend to be performed with the assistance of the main chain CONH atoms rather than the more variable or limited side chain atoms of the peptides presumed to exist then.

No MeSH data available.


Related in: MedlinePlus