Introduction to Protein Structure

Part I Basic Structural Principles
1. The Building Blocks
Proteins are polypeptide chains
The genetic code specifies 20 different amino
acid side chains
Cysteines can form disulfide bridges
Peptide units are building blocks of protein
structures
Glycine residues can adopt many different
conformations
Certain side-chain conformations are
energetically favorable
Many proteins contain intrinsic metal atoms
Conclusion
Selected readings
2. Motifs of Protein Structure
The interior of proteins is hydrophobic
The alpha (a) helix is an important
element of secondary structure
The a helix has a dipole moment
Some amino acids are preferred in
a helices
Beta (b) sheets usually have their b strands
either parallel or antiparallel
Loop regions are at the surface of
protein molecules
Schematic pictures of proteins highlight
secondary structure
Topology diagrams are useful for classification
of protein structures
Secondary structure elements are connected
to form simple motifs
The hairpin b motif occurs frequently in
protein structures
The Greek key motif is found in antiparallel
b sheets
The b-a-b motif contains two parallel
b strands
Protein molecules are organized in a structural
hierarchy
Large polypeptide chains fold into several
domains
Domains are built from structural motifs
Simple motifs combine to form complex motifs
Protein structures can be divided into
three main classes
Conclusion
Selected readings
3. Alpha-Domain Structures
Coiled-coil a helices contain a repetitive
heptad amino acid sequence pattern
The four-helix bundle is a common domain
structure in a proteins
Alpha-helical domains are sometimes large
and complex
The globin fold is present in myoglobin and
hemoglobin
Geometric considerations determine
a-helix packing
Ridges of one a helix fit into grooves of an
adjacent helix
The globin fold has been preserved during
evolution
The hydrophobic interior is preserved
Helix movements accommodate interior
side-chain mutations
Sickle-cell hemoglobin confers resistance
to malaria
Conclusion
Selected readings
4. Alpha/Beta Structures
Parallel b strands are arranged in barrels
or sheets
Alpha/beta barrels occur in many different
enzymes
Branched hydrophobic side chains dominate
the core of a/b barrels
Pyruvate kinase contains several domains,
one of which is an a/b barrel
Double barrels have occurred by gene
fusion
The active site is formed by loops at one
end of the a/b barrel