Helix formation and stability in a signal sequence

• Published in: Biochemistry (Easton) Vol. 28; no. 21; pp. 8554 - 8561
• Main Authors: Bruch, Martha D, McKnight, C. James, Gierasch, Lila M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17-10-1989
• Subjects: Amino Acid Sequence; Bacterial Outer Membrane Proteins; Chemical Phenomena; Chemistry, Physical; Circular Dichroism; Magnetic Resonance Spectroscopy; Molecular Sequence Data; N.M.R; Porins; Protein Conformation; Protein Sorting Signals; Receptors, Virus; signal peptides; Temperature
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00447a043

A detailed nuclear magnetic resonance analysis of the isolated LamB signal peptide (MMITLRKLPLAVAVAAGVMSAQAMA) under conditions defined by circular dichroism spectra to mimic the conformational distribution of this peptide in membranelike environments has provided a description of specific residue conformational preferences. This 25-residue long peptide in 20 mol % trifluoroethanol in water is in dynamic equilibrium between a helical and a more random conformation, and this equilibrium is shifted toward the more random structure as the temperature is raised. Part of the molecule, residues 10-18, exists in a stable helix at all temperatures studied (5, 25, and 50 degrees C). Propagation of the helix through the C-terminal end occurs at 25 degrees C, while the temperature must be lowered to 5 degrees C to observe any significant population of a helical conformation in the N-terminal region. These results argue that the Pro and Gly residues, which flank the helical segment, act to disfavor helix propagation on their N- or C-terminal sides, respectively. The influence of the Pro residue is stronger than that of the Gly. Furthermore, the most stable part of the helix in this signal peptide under the conditions studied is the hydrophobic core, which is the hallmark of functional signal sequences.