Manipulation of peptide conformations by fine-tuning of the environment and/or the primary sequence.
The widely observed phenomenon that peptides are capable of adopting multiple conformations in different environments suggests that secondary structure formation in a peptide segment is a process involving not only the peptide itself but also the surrounding solvent media. The influence of the primary sequence and the molecular environment on peptide conformations are now investigated using synthetic peptides of amino acid sequence H2N-(Ser-Lys)2-Ala-X-Gly-Ala-X-Gly-Trp-Ala-X-Gly-(Lys-Ser)3-OH, where X = Ile or Val. These two peptides, namely 3I (X = Ile) and 3V (X = Val), are found to lack defined secondary structure in aqueous buffer. However, discrete conformational states, e.g., alpha-helices and beta-sheets, are readily generated and interconverted for both peptides when the buffer is modulated with the addition of methanol, sodium dodecyl sulfate (SDS) micelles, or phospholipid vesicles. The role of the primary sequence in affecting peptide conformations is manifested in that peptides 3I and 3V, which differ respectively in their content of beta-branched Ile or Val residues, differ in their secondary structures at monomeric concentrations in 2 mM SDS and in mixed lipid vesicles of phosphatidic acid and phosphatidylcholine. The overall results suggest that peptide segments can be conformationally flexible entities poised to react to minor modulation in either the molecular environment or the primary sequence, a circumstance that may be relevant to protein functioning and folding.
Li
S C
SC
Division of Biochemistry Research, Hospital for Sick Children, Toronto, Ontario, Canada.
Kim
P K
PK
Deber
C M
CM
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D008081:Liposomes; D000432:Methanol; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D014867:Water
D008081:Liposomes; D010455:Peptides; D012996:Solutions; D014867:Water; D000432:Methanol