Protein backbone

1
Protein backbone

• Biochemical view
• basic repeating unit is NHCaHCO
• We can also look at repeating units from Ca to Ca
• Interesting properties
• Bond lengths almost equal in all groups, in all
  proteins
• Bond angles almost equal in all groups, in all
  proteins
• A Ca atom belongs to two units
• All atoms in an unit coplanar
• Preferable when describing structural properties

2
Protein backbone

• Geometric/Structural view polypeptide chain
  divided into
• Peptide units
• Ca atom and carboxyl group of residue i
• Amino group and Ca atom of residue i1
• Are rigid groups
• Rotation on bond C-N is prevented by energy
  barrier
• Peptide units are joined by covalent bonds
  between Ca atoms. Thus
• Peptides can rotate along 2 bonds
• N-Ca and Ca-C
• Two dihedral angles for each unit ? (Phi) and ?
  (Psi)
• Two degrees of freedom per unit
• Determine the conformation of the backbone

3
Dihedral angles and regular structures

• Repeating values of ? and ? along the main chain
  result in regular structure
• repeating values of ? -57o and ? -47o give a
  right-handed helical fold (a-helix)
• repetitive values of ??-110,-140 and
  ??110,135 give sub chains with conformations
  that allow interactions between nearby parallel
  segments (ß-sheet)
• Most combinations of ? and ? angles are not
  allowed
• Allowed conformations plotted as 2-D chart
• Ramachandran plot

4
Secondary Structure

• defined by patterns of hydrogen bonds between
  backbone amide groups
• sidechain-mainchain and sidechain-sidechain
  hydrogen bonds are irrelevant
• The amino acids in the interior/core of a
  globular protein have hydrophobic side chains
• Water soluble proteins fold to pack hydrophobic
  side chain into interior
• Results in hydrophobic core and hydrophilic
  surface
• The main chain must fold into interior, too
• Main chain is hydrophilic
• N--H hydrogen bond donor
• CO hydrogen bond acceptor
• These groups must be neutralized by formation of
  H bonds ? secondary structure
• Secondary structure
• a-helices
• ß-sheets
• form rigid and stable frameworks

5
a-Helix

• Righthanded coiled conformation
• backbone N-H group i4 forms hydrogen bonding
  with backbone C  O group i
• 3.6 residues per turn (5.4 Å, 1.5 Å per residue)
• Variations, with chain more loosely or tightly
  coiled are possible (i3 or i5 instead of i4)
  but not often
• backbone (f, ?) dihedral angles around
  (-60o,-45o)
• Sum of f and ? angles of consecutive residues
  about 105o
• Has between 4 to 40 residues
• All H bonds point in the same direction
• Aligned along helical axis
• Dipole moments for residues are aligned along
  axis
• Net dipole for a-helix ( at N-H end and at CO
  end)

6
Representations (cartoon, backbone trace, space
filling)
7
ß-sheets

• Combination of several regions of the chain (not
  chain adjacent) ß-strands
• Parallel all amino acids go in same direction
• Evenly spaced H bonds
• Antiparallel amino acids in successive strands
  alternate directions
• Alternate narrowly/widely spaced H bonds
• Mixed ß-sheet also exist
• Have twisted strands right-handed twist (always)
• ß-strand 5 to 10 residues long
• Almost fully extended

8
Representations (bond, cartoon, ribbon)
9
From secondary structure to structure

• Protein structure built from secondary
  structures
• Connected by loop regions
• Various lengths
• Irregular shape
• Are at the surface of the protein
• Reach in charged and polar residues
• Easier to predict!
• In homologous proteins almost always insertions
  and deletions occur in the loop regions.

10
Structure Motifs

• Secondary structures ? connected to form motifs
• a-helices and ß-sheets in a motif
• Adjacent in the 3-dimensional structure
• Connected bu loop regions
• Combinations of motifs and secondary structures ?
  domains

11

• Tertiary structure
• Arrangement of secondary structure
• Structural domains
• Quaternary structure
• More than one polypeptide folded together
• Native conformation direct consequence of
• primary structure
• chemical environment
• water based
• oily interior of a cell membrane
• So far, no reliable computational method exists
  to predict the native structure from the amino
  acid sequence

12
Structure Classes

• Protein structure ? four classes
• a-domains
• core built up only from a-helices
• ß-domains
• core built up only from (usually 2) antiparallel
  ß-sheets
• a/ß-domains
• mostly ß-a-ß motifs
• (mostly) parallel ß-sheets surrounded by
  a-helices
• aß-domains (few cases)
• antiparallel ß-sheet packed against a-helices