Tensile mechanics of alanine-based helical polypeptide: force spectroscopy versus computer simulations.
In nature, an alpha-helix is commonly used to build thermodynamically stable and mechanically rigid protein conformations. In view of growing interest in the mechanical rigidity of proteins, we measured the tensile profile of an alanine-based alpha-helical polypeptide on an atomic-force microscope to investigate the basic mechanics of helix extension with minimal interference from side-chain interactions. The peptide was extended to its maximum contour length with much less force than in reported cases of poly-L-Glu or poly-L-Lys, indicating that chain stiffness strongly depended on the physicochemical properties of side chains, such as their bulkiness. The low tensile-force extension originated presumably in locally unfolded parts because of spontaneous structural fluctuations. In 50% trifluoroethanol, the well-known helix-promoting agent, the rigidity of the sample polypeptide was markedly increased. Computer simulations of the peptide-stretching process showed that a majority of constituent residues underwent a transition from an alpha-helical to an extended conformation by overcoming an energy barrier around psi approximately 0 degrees on the Ramachandran plot. The observed lability of an isolated helix signified the biological importance of the lateral bundling of helices to maintain a rigid protein structure.
Afrin
Rehana
R
Biofrontier Center, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
Takahashi
Ichiro
I
Shiga
Kazuki
K
Ikai
Atsushi
A
D000409:Alanine / Q000737:chemistry*; D000595:Amino Acid Sequence; D001696:Biomechanical Phenomena; D002942:Circular Dichroism; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D019791:Guanidine / Q000494:pharmacology; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009930:Organic Chemicals / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011489:Protein Denaturation / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology; D012997:Solvents / Q000494:pharmacology; D013057:Spectrum Analysis; D013718:Tensile Strength
D009930:Organic Chemicals; D010455:Peptides; D012997:Solvents; D012965:Sodium Chloride; D019791:Guanidine; D000409:Alanine