helix-coil transition theory: from biophysics to biochemistry via probability ~ lauraine dalton
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Helix-Coil Transition Theory: from biophysics to biochemistry via probability ~ Lauraine Dalton. Protein primary, secondary, tertiary structure. Alpha helix secondary structure properties. - PowerPoint PPT PresentationTRANSCRIPT
Helix-Coil Transition Theory: from biophysics to biochemistry via probability
~ Lauraine Dalton
• Protein primary, secondary, tertiary structure.
• Alpha helix secondary structure properties.
• Historical development of helix-coil transition theory (HCTT); from chemical physics to empirical biochemistry.
• Helices at work; selected examples.
The peptide bond has partial pi character; its geometry is planar.
C is a member of two planes.
Rotation about Ca sigma bonds:
dihedral angles phi and psi
psiphi
psiphi
(yellow arcs)
Ramachandran plot of allowed dihedral
angles. Steric clashes of side chains limit rotation.
Hydrogen bond network of the alpha helix
Helix-coil transition, a
disruptive view of unraveling
Nucleation involves adjustment of 6 dihedral angles; elongation, 2
Nucleation (difficult) & Propagation (facile)
The equilibrium constant for nucleation (sigma) is typically 1000 times lower than for propagation (s).
(…cccchhhcccc….) s = (…ccccccccccc….)
and the equilibrium constant (statistical weight) for adding another helical segment at the end of a stretch of helical residues is
(….ccchhhhhhhhccc…) s = (….ccchhhhhhhcccc…)
Typical values of and s is approx 0. 001 * s
Residue s RemarksGlycine 1E-5 0.62 Glycineexceptional rangeofφ,ψAlanine 8E-4 1.06 SmallvolumeofsidechainSerine 7.5E-5 0.79 Likealaninebutone-OHLeucine 33E-4 1.14 Flexibl e hydrocarbonsidechain
Helix macro dipole increases stability for long helices (supports elongation s)
Zimm-Bragg and Lifson-Roig concepts of weighting
Sharpness of the transition,
as calculated by Schellman in 1958A = coexistence of
hhh and ccc intermediate states;
B = h or c all or none
C = infinitely long
helix
Chou-Fasman “rules” of biochemistry (probabilities)
Helix initation and termination in proteins
• J & D Richardson focused on Ncap and Ccap in analysis of 215 helical segment in known structures.
• Current view is that Ncap motif consists of four residues S(T)XXE(D) = hydroxyl-XX-carboxylate.
• Carboxylate (-) interacts favorably with helix macro dipole (+)
• Ccap contributors are misfits; P (bulky ring) and G (no side chain; 2 H; very flexible)
Helices at work; stable structures perform mechanical tasks in lipid bilayer
Biotin (+Avidin) measurement tool