title: On the split personality of penultimate proline.
abstract: The influence of the position of the amino acid proline in polypeptide sequences is examined by a combination of ion mobility spectrometry-mass spectrometry (IMS-MS), amino acid substitutions, and molecular modeling. The results suggest that when proline exists as the second residue from the N-terminus (i.e., penultimate proline), two families of conformers are formed. We demonstrate the existence of these families by a study of a series of truncated and mutated peptides derived from the 11-residue peptide Ser(1)-Pro(2)-Glu(3)-Leu(4)-Pro(5)-Ser(6)-Pro(7)-Gln(8)-Ala(9)-Glu(10)-Lys(11). We find that every peptide from this sequence with a penultimate proline residue has multiple conformations. Substitution of Ala for Pro residues indicates that multiple conformers arise from the cis-trans isomerization of Xaa(1)-Pro(2) peptide bonds as Xaa-Ala peptide bonds are unlikely to adopt the cis isomer, and examination of spectra from a library of 58 peptides indicates that ~80% of sequences show this effect. A simple mechanism suggesting that the barrier between the cis- and trans-proline forms is lowered because of low steric impedance is proposed. This observation may have interesting biological implications as well, and we note that a number of biologically active peptides have penultimate proline residues.
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, IN, 47405, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Glover
authors.forename: Liuqing
authors.initials: L
authors.lastname: Shi
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Fuller
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Arnold
authors.forename: Predrag
authors.initials: P
authors.lastname: Radivojac
authors.forename: David E
authors.initials: DE
authors.lastname: Clemmer
mesh_terms: D000595:Amino Acid Sequence; D007536:Isomerism; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011392:Proline / Q000737:chemistry*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins; D011392:Proline