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Ionized Trilysine: A ModelSystem for Understandingthe Nonrandom Structure of Poly-l-lysine and Lysine-ContainingMotifs in Proteins.

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Title: Ionized Trilysine: A ModelSystem for Understandingthe Nonrandom Structure of Poly-l-lysine and Lysine-ContainingMotifs in Proteins.
Authors: Verbaro, Daniel J.1, Mathieu, Daniel1, Toal, Siobhan E.1, Schwalbe, Harald1, Schweitzer-Stenner, Reinhard1
Source: Journal of Physical Chemistry B. Jul2012, Vol. 116 Issue 28, p8084-8094. 11p.
Subjects: Lysine derivatives, Mathematical models, Protein analysis, Amino acids, Conformational analysis, Nuclear magnetic resonance spectroscopy
Abstract: It is now well-established that different amino acidresidues canexhibit different conformational distributions in the unfolded stateof peptides and proteins. These conformational propensities can bemodulated by nearest neighbors. In the current study, we combinedvibrational and NMR spectroscopy to determine the conformational distributionsof the central and C-terminal residues in trilysine peptides in aqueoussolution. The study was motivated by earlier observations suggestingthat interactions between ionized nearest neighbor residues can substantiallychange conformational propensities. We found that the central lysineresidue predominantly adopts conformations that are located at theupper border of the upper left quadrant of the Ramachandran plot andthe left border of the polyproline II region. We term this type ofconformation deformed polyproline II (pPIId). The structuresof less populated subensembles of trilysine resemble are comparablewith structures at the i 1 position of type I andtype II β-turns. For the C-terminal residue, however, we obtaineda mixture of polyproline II, β-strand, and right-handed helicalconformations, which is typical for lysine residues in alanine- andglycine-based peptides. Our data thus indicate that the terminal lysinesmodify and restrict the conformational distribution of the centrallysine residue. DFT calculations for ionized trilysine and lysyllysyllysylglycinein vacuo indicate that the pPIIdis stabilized by a ratherstrong hydrogen bond between the NH3芺of the central lysine and the carbonyl group of the C-terminal peptide.This intramolecular hydrogen bonding induces optical activity in theC-terminal CO stretching vibration, which leads to an unusual andrelatively intense positive Cotton band. Additionally, we analyzedthe amide I′ band profile of ionized triornithine in water.Ornithine is structurally similar to lysine in that its side chainis terminated with an amino group; however, the side chain of ornithineis shorter than lysine’s side chain by one methylene group.We found that the conformational distribution of the central ornithinein this peptide must be very similar to that of the central lysineresidue in trilysine. This suggests that the ionized ammonium group,which lysine and ornithine side chains have in common, is the maindeterminant of their conformational propensities at the central positionin the respective tripeptides. The results of a DFT-based geometryoptimization confirm this notion. In principle, our results suggestthat lysine-rich segments in unfolded/disordered proteins and peptidescan switch between different types of local order, i.e., an extendedpPIId-like conformation and transient turns. However, forlonger polylysine segments nonlocal interactions between side chainsmight impede the formation of turns, thus enabling the formation ofpPIId-helix segments. [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
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Abstract:It is now well-established that different amino acidresidues canexhibit different conformational distributions in the unfolded stateof peptides and proteins. These conformational propensities can bemodulated by nearest neighbors. In the current study, we combinedvibrational and NMR spectroscopy to determine the conformational distributionsof the central and C-terminal residues in trilysine peptides in aqueoussolution. The study was motivated by earlier observations suggestingthat interactions between ionized nearest neighbor residues can substantiallychange conformational propensities. We found that the central lysineresidue predominantly adopts conformations that are located at theupper border of the upper left quadrant of the Ramachandran plot andthe left border of the polyproline II region. We term this type ofconformation deformed polyproline II (pPIId). The structuresof less populated subensembles of trilysine resemble are comparablewith structures at the i 1 position of type I andtype II β-turns. For the C-terminal residue, however, we obtaineda mixture of polyproline II, β-strand, and right-handed helicalconformations, which is typical for lysine residues in alanine- andglycine-based peptides. Our data thus indicate that the terminal lysinesmodify and restrict the conformational distribution of the centrallysine residue. DFT calculations for ionized trilysine and lysyllysyllysylglycinein vacuo indicate that the pPIIdis stabilized by a ratherstrong hydrogen bond between the NH3芺of the central lysine and the carbonyl group of the C-terminal peptide.This intramolecular hydrogen bonding induces optical activity in theC-terminal CO stretching vibration, which leads to an unusual andrelatively intense positive Cotton band. Additionally, we analyzedthe amide I′ band profile of ionized triornithine in water.Ornithine is structurally similar to lysine in that its side chainis terminated with an amino group; however, the side chain of ornithineis shorter than lysine’s side chain by one methylene group.We found that the conformational distribution of the central ornithinein this peptide must be very similar to that of the central lysineresidue in trilysine. This suggests that the ionized ammonium group,which lysine and ornithine side chains have in common, is the maindeterminant of their conformational propensities at the central positionin the respective tripeptides. The results of a DFT-based geometryoptimization confirm this notion. In principle, our results suggestthat lysine-rich segments in unfolded/disordered proteins and peptidescan switch between different types of local order, i.e., an extendedpPIId-like conformation and transient turns. However, forlonger polylysine segments nonlocal interactions between side chainsmight impede the formation of turns, thus enabling the formation ofpPIId-helix segments. [ABSTRACT FROM AUTHOR]
ISSN:15206106
DOI:10.1021/jp303794s