Transcript Protein structure

Protein Structure 1
Primary and Secondary Structure
Proteins fold into the local minimum free energy structure
defined by their primary sequence.
The native structure may not be the global free energy structure.
Polypeptide chains can assume an infinite number of potential
structures (Levinthal’s Paradox). The physical chemistry of the
peptide bond and steric hindrance between the peptide bond
elements restrict the potential structures assumed by a
polypeptide to a finite number of structures.
Hierarchy of Protein Structure
Primary sequence- The amino acid sequence of a polypeptide, listed from
N-terminus to C-terminus.
Secondary structure- Recurring structural feature of proteins stabilized
exclusively by hydrogen bonds between peptide bond elements.
Supersecondary structure- Recurring structural feature of proteins
composed of two or more secondary structural elements.
Domain- A segment of protein structure that is autonomously stable.
Tertiary structure- A stable, independent protein encoded by a single gene.
Quaternary structure- A complex structure composed of two or more tertiary
structure subunits.
The Electronegativity of the O and N of the Peptide Bond
Results in a Dipole
Peptide Bonds Favor the trans Configuration Except
When Proline is Present
poly-alanine (trans:cis = 2500:1)
alanyl-prolyl (trans:cis = 4:1)
In cells, prolyl peptide isomerization is catalyzed by Prolyl isomerase.
Resonance in the Peptide Bond Results in Planarity of the
Peptide Bond
Psi angle
Phi angle
Polypeptides behave as a series of plates hinged at C.
Ramachandran Plots Define the Allowable Structures
Assumed by a Polypeptide Chain
di-Alanine
di-Glycine
(hard sphere approximation)
Proline dihedral angels observed
in protein structures
after Ramachandran et al. J. Mol. Biol. 7, 95-99 (1963)
di-Alanine
(molecular dynamics calculation)
Plot of phi and psi angles for 2500
residues in 13 proteins
Types of Secondary Structures
Repeating Structures Form Helices
Alpha, 310, and Pi Helices
Helical wheel plot revealing
amphipathic nature of helix
310 helix
 helix
 helix
Cylindrical plot revealing
alignment of side chains
Side Chain Interactions Provide Additional Stability to
Helices and Signal the Limits of Helix Formation
Table of helical propensities
Parallel and Anti-parallel Beta Sheets
anti-parallel
parallel
The Gly-X-Y Repeat Sequence is Essential for
Collagen Triple Helix Formation
poly-proline
collagen triple helix
Reverse Turns Connect Segments of Anti-parallel
Beta Sheets
Type 1 reverse turn
Type 2 reverse turn
310 helix
Always glycine