George Posadas II

11821477

1. Cite the unique structural features (without writing the full structure) and
biological functions of each of the following peptides: (2 pts)

(a) Oxytocin
 They are peptides with nine amino acids. The are released
during labor in large amounts after the distention of the cervix
and vagina. Oxytocin is a neuropeptide released during birth
and lactation, but also in response to social interaction and
stressors.

(b) Vasopressin

● Polypeptide containing nine amino acids with a disulfide bridge

between cysteine residues
● small, nonapeptide hormone, synthesized in the
hypothalamus, and released into the circulation from the
posterior pituitary gland
● Antidiuretic hormone
● Released when body is dehydrated and causes kidneys to
conserve water which affects urine concentration

(c) Enkephalins

● pentapeptide involved in regulating nociception in the body

● Two forms of Enkephalin: one containing leucine and other
methionine generated from a precursor protein called
proenkephalin by posttranslational proteolytic cleavage
● Has a powerful painkilling effect

(d) Glutathione

● Tripeptide comprises three amino acids, which are cysteine,

glutamic acid and glycine. They are present in most
mammalian tissue
● A detoxifying agent which fros a soluble compound, the toxin
that can be excreted through urine or the gut

2. Briefly describe the role of the heat shock protein Hsp70 in protein folding. (1 pt)

The HSP70 heat-shock proteins are molecular chaperones that assist other
proteins in their folding, transport and assembly into complexes. The Hsp70
system interacts with extended peptide segments of proteins as well as
partially folded proteins to cause aggregation of proteins in key pathways to
deregulate activity.
George Posadas II
11821477

3. What are protein domains? How different are they from protein motifs? (2 pts)

A motif is a short-conserved sequence pattern associated with distinct

functions of a protein or DNA. It is often associated with a distinct structural
site performing a particular function. A typical motif, such as a Zn-finger motif,
is ten to twenty amino acids long. A domain is also a conserved sequence
pattern, defined as an independent functional and structural unit. Domains are
normally longer than motifs. A domain consists of more than 40 residues and
up to 700 residues, with an average length of 100 residues. A domain may or
may not include motifs within its boundaries. Examples of domains include
transmembrane domains and ligand-binding domains.

4. What structural and functional advantages do proteins gain by associating to

form quaternary structures? (2 pts)
1) Stability: reduces the protein's surface-to-volume ratio

2) Genetic economy and efficiency: less DNA is required to code monomer

3) Bringing catalytic sites together

4) Cooperativity (e.g., with haemoglobin, the first molecule to bind makes the
next molecules easier to bind); binding at one site increases binding at other
sites

5) The interaction between subunits allows for the subunits to influence each
other's behaviours.

5. Discuss (as comprehensively but as concisely as possible) the role of protein

folding in any (one) of the following diseases. Suggest an accepted
appropriate treatment for the disease. Cite your references. (3 pts)

Gaucher’s disease

A mutation of the GBA1 gene encoding for glucocerebrosidase, the lysosomal

enzyme. The genetic alterations in GBA1 lead to quantitative losses of GCase
and accumulation of toxic mounds of glucocerebroside. These mutations
causes protein to misfold and for premature degradation

Both gene knockdown and pharmacologic inhibition of Hsp27 increased

GCase levels in patient-derived fibroblasts. Reduction of Hsp27 may
circumvent premature protein degradation and represents a viable potential
therapeutic strategy in the treatment of protein misfolding disorders.

Instead of catastrophic loss of intrinsic enzymatic catalytic function, most

GBA1 mutations lead to changes in the natural conformation of the peptide
during protein folding, followed by retention within the endoplasmic reticulum
(ER) . Subsequently, the unnatural peptide conformation affects chaperone
recognition, which then stimulates premature protein degradation via
mechanisms, involving c-cbl associated proteasomal complexes and the E3
ligases Parkin and Itch
George Posadas II
11821477

An enzyme replacement therapy which can replace the deficient enzyme to

artificial one, miglustat or eliglustat an oral medication to interfere with the
buildup of fatty substances, osteoporosis drugs to help rebuild bone that is
weakened and bone marrow transplant which removes blood-forming cells
that have been damaged.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313839/#:~:text=Gaucher%20disease
%20(GD)%20is%20an,misfolding%20and%20subsequent%20premature
%20degradation.

https://www.mayoclinic.org/diseases-conditions/gauchers-disease/diagnosis-
treatment/drc-20355551