TUTORIAL ON PEPTIDE AND PROTEIN STRUCTURE

II. SECONDARY STRUCTURE

                                                Copyright: J. E. Wampler, 1996

Secondary Structure is the local structure which is typically recognized by specific backbone Torsion Angles and specific mainchain Hydrogen Bond pairings.

This section covers:

Definition of the torsion angles, phi, psi and omega.
Rotation about the amide bond.
Ramachandran plots and regular structure.
H-bonding patterns and regular structure.
Details of Alpha Helix.
Details of Beta Sheets.
Other structures with repetitive phi,psi angles.
Turns are identifiable structures too.
Folding by Rotation about Single Bonds:

Since bond length and angles are fairly invariant in the known protein structures, the key to protein folding lies in the torsion angles of the backbone.

A torsion angles is defined by 4 atoms, A, B, C and D.

When atoms A, B, C and D are mainchain atoms (ie. the carboxylic carbon, C1; the alpha carbon, C2 or C-alpha; and the amide group nitrogen, N), There are THREE repeating torsion angles along the backbone chain called phi, psi and omega.

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The OMEGA angle tends to be planar (0 or 180o) due to delocalization of the carbonyl pi electrons & the nitrogen lone pair.

Trans is generally favored over cis:


Only 116 (0.36%) of 32,539 angles in 154 X-ray structures were found to be cis (Stewart et al. 1990).

However...... some specific bonds are often cis, eg.

Tyr-Pro (25%), Ser-Pro (11%), X-Pro (6.5%)
This leaves phi and psi for flexible folding of the chain. However, steric conflicts limit even these angles as well.

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Plot of Psi vs Phi often called a Ramachandran plot (after G. N. Ramachandran) or conformational map.

Repeating values of phi and psi along the chain result in regular structure. For example, repeating values of phi ~-57o and psi ~-47o give a right-handed helical fold (the alpha-helix). The structure of cytochrome C-256 shows many segments of helix and the Ramachandran plot shows a tight grouping of phi,psi angles near to -50,-50.

Similarly, repetitive values in the region of phi = -110 to -140 and psi = +110 to +135 give extended chains with conformations that allow interactions between closely folded parallel segments (beta sheet structures). The structure of plastocyanin is composed mostly of beta sheets and the Ramachandran plot shows a broad range of values in the -110,+130 region.

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The hydrogen bond is a key concept in describing the selectivity and stability of protein and nucleic acid structures. It involves three atoms, a donor electronegative atom, D, to which the hydrogen is bound (ie. N, O, or S in proteins) and an acceptor electronegative atom, A, in close proximity.

The D-H interaction is characterized by:

Polarization due to electron withdrawal from the hydrogen to D giving D partial negative charge and the H a partial positive charge.

These separated partial charges make the D-H bond a dipole.

Shortened D-H bond distance (typically ~ 1 Angstrom).

A decreased Hydrogen radius (from 1.2 to ~ 1 Angstrom).

The proximity of the Acceptor A causes further charge separation.

The result is:

Closer approach of A to the hydrogen (typically ~ 2 Angstroms).

Higher interaction energy than a simple van der Waals interaction.

A point-charge to dipole type interaction which...

"reaches" further (~1/(distance)3 or 1/(distance)2) than a typical van der Waals interaction (~1/(distance)6)

AND

has angle dependence (a point-charge to dipole interaction falls off as the cosine of the angle that the A to H vector makes to the D-H vector).

In proteins and nucleic acids the predominant regular structures are also characterized by repeating hydrogen bond opportunities. With protein secondary structure, regularly spaced intrachain hydrogen bonding is seen.

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The alpha helix is characterized by hydrogen bonds along the chain, almost co-axial. When the phi,psi angles are in the nominal range:

- the mainchain carbonyl C=O of each residue H-bonds to the amide N-H 4 residues along the chain

- there are about 3.6 residues per turn of the helix

- the sidechain are projected outward

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The beta sheet is characterized by hydrogen bonds crossing between chains. Beta sheet strands are:

- not fully extended (phi,psi = -180,180) due to sidechain steric inteferences

- the chain is slightly "puckered" so that the sheet is sometimes said to be "pleated"

- two H-bonding chains may run parallel or antiparallel

- on average parallel (both chains running N-terminal to C-terminal in the same direction) sheet chains have phi,psi = -119,113.

- on average antiparallel sheet chains have phi,psi - -139,135.

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Repeating phi,psi angles always lead to some type of regular structure providing that it is stericly allowed. In addition to the alpha-helix and the beta sheets, there are several other "named" structures: 

      Name            phi     psi      Comments                 
------------------- ------- ------- ---------------------------------
alpha-L              57      47      left-handed alpha helix.
3-10 Helix          -49     -26      right-handed.
pi helix            -57     -80      right-handed.
Type II helices     -79     150      left-handed helicies
                                     formed by polyglycine
                                     and polyproline.
Collagen            -51     153      right-handed coil formed
                                     of three left handed 
                                     helicies.

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Several definable turns and bends in protein structure have been recognized and classified either by the relationship between the phi,psi angles of the residues in the turn or the hydrogen bonding of their amide N-H and carbonyl-oxygen atoms. The tightest turns involve only 3 residues with hydrogen bonding between the carbonyl of the 1st residue (N-terminal end) and the N-H of the 3rd residue. These turns are referred to as gamma turns. The center residue has phi,psi values near 80,-65 (or -80, 65 for inverse gamma turns), a region of the Ramachandran plot not typically occupied.

Turns involving four (4) residues are more common with hydrogen bonding from the carbonyl of residue 1 to the N-H of residue 4. One class of these turns is called beta-turns, typically found at turns of beta-sheet structure and designated by Roman numerals. Some of their characteristics are: 

              Residue 2  Residue 3
Designation    Phi,Psi    Phi,Psi      Comments
------------- ---------- ---------
   I           -60,-30     -90,0    Most common type.
   II          -60,120      80,0  
   III         -60,-30     -60,-30  Like 3,10 helix.
   IV*
   V           -80,80       80,-80
   VIa         -60,120     -90,0    2-3 peptide bond
                                    is cis, residue
                                    3 is proline.
   VIb        -120,120     -60,0    2-3 peptide bond
                                    is cis, residue
                                    3 is proline.
   VII**
   VIII        -60,-30    -120,120
---------------------------------------------------------------
*  Type IV is for turns not otherwise classified
** Type VII is a bend recognized by psi(2)~180 and phi(3)<60 or
   by psi(2)<60 and phi(3)~180.  

Favorable and (unfavorable) Residues in Beta-turns by Position:

  Type     Residue 1   Residue 2   Residue 3   Residue 4
--------  ----------- ----------- ----------- -----------
   I       Asp, Asn,      Pro         (Pro)       Gly
           Ser, Cys

   II      Asp, Asn,      Pro       Gly, Asn      Gly
           Ser, Cys

   VIa                                 Pro

   VIb                                 Pro
---------------------------------------------------------

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Go back to Introduction.
Go back to Part I.
Continue to Part III.