Advanced Certificate in
Principles of Protein Structure
Draft Questions for 3 hr Examination Paper September 1996
4 Questions to be answered. (Between 8 and 12 should be set).
1.0 Describe the experimental work on fibrous proteins which led to
models for the alpha-helix and beta-sheet. How has subsequent structure
analysis of globular proteins contributed to our understanding of secondary
1.1 What are the essential features of the Pauling-Corey alpha-helix
and beta-sheet? What factors lead to the distortion of alpha-helices
in proteins? Why are all-parallel beta-sheets thought to be less
stable than antiparallel sheets?
(a) Sketch a Ramachandran plot indicating the alphaR, beta and alpa
L regions. Why might the distribution of main chain torsion angles
observed in the protein structures differ slightly from that predicted
2.0 Outline the applications of NMR spectroscopy to the study of three
of the following topics:
(a) primary structure of proteins
(b) secondary structure of proteins
(c) tertiary structure of proteins
(d) protein-drug interactions
(e) protein-nucleic acid interactions
(f) protein mobility and dynamics
2.1 How might NMR spectroscopy be used to investigate:
(a) the structure and conformations of proteins
(b) protein-ligand interactions
Outline the principles of site-directed mutagenesis.
4.0 Discuss the following issues in the investigation of metalloenzymes:
(a) determination of the total amount of metal present
(b) identification of the metal
(c) determination of the oxidation state of the metal
(d) identification of the types and numbers of coodinated ligands.
4.1 Discuss the structure and mechanism of metalloproteins and metalloenzymes
with particular reference to iron and copper.
Describe the 3-dimensional structural organisation of proteins involved
in striated muscle contraction.
How do signals get into cells and evoke a specific biological response?
Illustrate your answer with examples of well-known signal transduction
systems, explaining the mechanisms of transduction that are currently understood.
7.0 How are nucleotide sequences of DNA recognised specifically by
7.1 Describe the commonly occurring DNA binding motifs in proteins
indicating which parts, if any, are involved in direct recognition of the
Discuss the 3-dimensional structures of the eye-lens proteins and their
organization in the eye-lens.
9.0 A two-stranded beta-sheet is an unlikely motif for the transmembrane
part of a membrane protein. Explain the reason for this and
discuss what is a more likely type of motif for strands of beta-structure
to adopt in this environment and why.
9.1 One structural motif that appears to be common to a number of membrane
proteins is the seven helical bundle. Discuss examples
of membrane proteins that have this type of motif and for one of
these briefly describe its function.
10.0 Write an essay on icosahedral virus structures, including a discussion
of the role of quasi-equivalence.
(a) Describe the structure of icosahedral viruses in general, including
the distinction between T=1 and T=3 viruses.
(b) How is Tomato Bushy Stunt Virus able to use only a single
coat protein to produce quasi-equivalent sites?
(c) Discuss how rhinovirus is more effective in evading immune
surveillance than is the polio virus.
11.0 Why are globular proteins only marginally stable in terms of
DeltaGfolding despite the numerous interactions which maintain their
tertiary structures? What theories have been proposed to account
for the speed with which the polypeptide folds to its native conformation?
11.1 How are non-covalent interactions involved in stabilising proteins?
Use myoglobin to illustrate how the same forces allow proteins to bind
ligands. What are the thermodynamic principles behind the introduction
of disulphide cross-links to increase a proteinís stability?
Describe the process of transcription in E. coli.
13.0 Compare the 3-dimensional structures of antibody molecules and
MHC proteins. How do their antigen-binding sites differ?
13.1 How is antibody diversity generated and how are the sequence variations
accommodated by the structure?
13.2 Describe the 3-dimensional structure of antibody molecules and
show how the antigen combining sites are formed. How in structural
terms can the antibody population recognise a vast range of antigens?
14.0 Collagen is an example of a protein for which post-translational
modification is essential for producing functioning molecules. Discuss
the three different types of post-translational modifications to collagen
with respect to the nature of the modification and the structural and functional
consequences of the modification.
14.1 Collagen is an excellent example of a molecule that can
be found in a number of different types of biomolecular organisations.
Discuss the structure of collagen and the post-translational modifications
that result in alternate types of molecular associations which produce
structures suited to different functions.
Classify the glycoproteins according to structure. Discuss critically
the role of glycoproteins in cellular recognition phenomena.
Use myoglobin and haemoglobin as examples to discuss the structural
basis of ligand binding cooperativity in proteins.
Discuss tertiary organisation in proteins.
Why do glycine and proline residues often occur in irregular regions
of globular protein structure?
Discuss the quaternary structure of oxyhaemoglobin and deoxyhaemoglobin
and how they differ.
Describe the 3-dimensional structure and function of a enzyme of your
choice. Briefly describe how the catalytic mechanism was elucidated.
Discuss the major classes of proteinase and their characteristics.
Discuss the important characteristics which distinguish the naturally-occurring
Discuss critically, with examples the terms:
as they relate to protein sequence comparisons.
(b) percentage sequence identity