On the split personality of penultimate proline.
Matthew S Glover1, Liuqing Shi, Daniel R Fuller
1Department of Chemistry, Indiana University, Bloomington, IN, 47405, USA.
Journal of the American Society for Mass Spectrometry
|December 16, 2014
Summary
Penultimate proline residues in peptides induce multiple conformations due to cis-trans isomerization. This structural diversity, observed in ~80% of sequences, may impact peptide biological activity.
Area of Science:
- Biochemistry
- Structural Biology
- Analytical Chemistry
Background:
- The conformation of peptides is crucial for their biological function.
- Proline residues are known to influence peptide structure due to their unique cyclic side chain.
- The specific positioning of proline, particularly near the N-terminus, warrants further investigation.
Purpose of the Study:
- To investigate the conformational impact of proline position in polypeptide sequences.
- To determine if a penultimate proline residue influences peptide structure.
- To elucidate the mechanism behind proline-induced conformational diversity.
Main Methods:
- Ion mobility spectrometry-mass spectrometry (IMS-MS) was employed to analyze peptide conformations.
- Amino acid substitutions were systematically introduced to probe structural influences.
- Molecular modeling was utilized to understand conformational dynamics.
- A library of 58 peptides was analyzed to assess the prevalence of the observed effect.
Main Results:
- Peptides with a penultimate proline residue consistently form two distinct families of conformers.
- Multiple conformations were observed in all tested peptides containing a penultimate proline.
- Cis-trans isomerization of the Xaa(1)-Pro(2) peptide bond was identified as the primary source of conformational multiplicity.
- ~80% of the analyzed peptide sequences exhibited this phenomenon.
Conclusions:
- The presence of a penultimate proline residue significantly increases peptide conformational heterogeneity.
- A low steric impedance mechanism likely facilitates cis-trans proline isomerization.
- The conformational flexibility induced by penultimate proline may have implications for the biological activity of peptides.
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