There are four levels of protein structure: 1) primary - linear sequence of amino acids 2) secondary - regular patterns formed by primary structure folding 3) tertiary - completely folded polypeptide with one or more domains 4) quaternary - association of multiple poly

Chapter 4 - Proteins
Proteins can be classified as either:
1) globular - spherical; water-soluble molecules with a hydrophobic interior
and hydrophobic surface; have mostly functional roles in the cell, e.g.
enzymes
2) fibrous - made into threads or cables with repeating units; water-insoluble
molecules that provide mechanical or structural support, e.g. keratin
and collagen
Protein Structure
peptides; not found in all proteins
PRIMARY STRUCTURE
peptide group - bond plus 4 groups
Bond between carbonyl carbon and nitrogen shorter than normal, but longer than
C=N bonds ---> partial double bond character ---> no free rotation around bond --->
bond is planar.
Peptide group can exist in cis or trans conformation --> nearly all in trans because of steric
hinderance.
There is rotation around N-Cbond (phi) and C-C bond ( psi). Figure 4.8 shows how
bond angles are measured.
Conformation of peptide group can be described by and

Only certain angles are permitted. Are shown in a Ramachandran plot ---> also shows
recognizable conformations. (Figure 4-9)
SECONDARY STRUCTURE
There are two common types of secondary structure:
1) -helix
Most common.
Can be described by pitch (distance for 1 turn of helix) and rise (distance/a.a.
residue).
2
Can be right or left-handed, but all right-handed.
Pitch = 0.54 nm ---> 3.6 a.a.
Rise = 0.15 nm
Main chain is core, with R-groups sticking out.
Stabilized by H-bonds between carbonyl oxygen and amide hydrogen 4 residues
toward C- terminus.
Some a.a. residues commonly found in -helices (alanine), whereas some a.a.
destabilize helix (e.g. glycine; lots of rotation).
Can have variation called 310 helix (right handed) - carbonyl oxygen H-bonds with
amide hydrogen 3 residues towards C-terminus ---> tighter ring structure with 10
atoms rather than 13, 3 residues/turn and longer pitch --> less stable, but usually
only a few residues in length.
2) -structures
-strands (almost fully extended helix) and -sheets (multiple strands in sheets
or layers)
Stabilized by H-bonds between carbonyl oxygens and amide hydrogens on adjacent ß
strands.
Can be arranged in either parallel (same N-C direction) or anti-parallel.
R-groups alternately point above and below plane when viewed in 3-D (Figure 4-16).
Globular proteins contain regions of structure.
Loops and Turns (nonrepetitive regions)
Cause directional change in the polypeptide backbone.
Bond angles are constrained, so that only certain directional changes are permitted.
Loops are often hydrophilic residues found on protein surfaces, where they H-bond with
water molecules.
Loops with about 5 a.a. residues are called turns.
Most common type of tight turn is a turn, which connects different antiparallel strands.
There are other types of turns and all hydrogen bond with other portions of the protein to
stabilize secondary structure.


3
TERTIARY STRUCTURE
Results from the folding of a polypeptide into a closely packed three-dimensional structure.
Amino acids that are far apart in the primary structure are brought together to have side
chain interactions.
Tertiary structure is stabilized primarily by noncovalent interactions, mostly hydrophobic
effects.
Disulfide bridges also contribute to tertiary structure.
Motifs (supersecondary structures)
Combinations of helicesstrands, and loops.
Often have a particular function, such as a protein binding site.
Different types include:
1) helix-loop-helix – found in calcium-binding proteins
2) coiled coil – leucine zipper in transcription proteins
3) helix bundle
4) unit
5) hairpin – connecting two antiparallel strands
6) meander – connecting multiple strands
7) Greek key – sheet with four antiparallel strands
8) sandwich – strands stacked on top of one another
Domains
Composed of several independently folded compact units.
May be a combination of motifs
Each domain contains various elements of secondary structure.
Domains are usually connected by loops, but bound to each other through R-group
interactions.