Molecular biology of protein folding. Pt. A

I. Introduction .................................................................................. 2 A. Structure of the a‐Helix ............................................................... 2 B. Capping Motifs.......................................................................... 4 C. Metal Binding ........................................................................... 4 D. The 310‐Helix ............................................................................ 6 E. The p‐Helix .............................................................................. 6 II. Design of Peptide Helices ................................................................. 7 A. History .................................................................................... 7 B. Host–Guest Studies .................................................................... 8 C. Helix Lengths............................................................................ 8 D. The Helix Dipole ....................................................................... 8 E. Acetylation and Amidation ........................................................... 10 F. Side‐Chain Spacings ................................................................... 10 G. Solubility.................................................................................. 10 H. Concentration Determination ....................................................... 11 I. Design of Peptides to Measure Helix Parameters............................... 12 J. Helix Templates......................................................................... 13 K. Design of 310‐Helices.................................................................. 13 L. Design of p‐Helices .................................................................... 15 III. Helix–Coil Theory........................................................................... 15 A. Zimm–Bragg Model.................................................................... 16 B. Lifson–Roig Model..................................................................... 16 C. The Unfolded State and Polyproline II Helix .................................... 19 D. Single‐Sequence Approximation .................................................... 20 E. N‐ and C‐Caps .......................................................................... 20 F. Capping Boxes .......................................................................... 21 G. Side‐Chain Interactions ............................................................... 21 H. N1, N2, and N3 Preferences......................................................... 21 I. Helix Dipole ............................................................................. 22 J. 310‐ and p‐Helices ...................................................................... 22 K. AGADIR ................................................................................. 23 L. Lomize–Mosberg Model.............................................................. 24 M. Extension of the Zimm–Bragg Model.............................................. 25 N. Tertiary Interactions ................................................................... 25 IV. Forces Affecting a‐Helix Stability........................................................ 25 A. Helix Interior ............................................................................ 25 B. Caps ....................................................................................... 29 C. Phosphorylation......................................................................... 32 D. Noncovalent Side‐Chain Interactions .............................................. 32 Progress in Molecular Biology Copyright 2008, Elsevier Inc. and Translational Science, Vol. 83 1 All rights reserved. DOI: 10.1016/S0079-6603(08)00601-6 0079-6603/08 $35.00 E. Covalent Side‐Chain Interactions................................................... 33 F. Capping Motifs.......................................................................... 33 G. Ionic Strength ........................................................................... 35 H. Enthalpy Change for the Helix–Coil Transition ................................. 36 I. Trifluoroethanol ......................................................................... 37 J. pKa Values................................................................................ 37 K. Relevance to Proteins.................................................................. 38 References .................................................................................... 38