Assignment 1 due October 24
This exercise is to further familiarize you with the diverse functions of
proteins, especially in context of our course topics, as well as their
role in disease.
To earn full credit (20 pts) you must:
Work independently,
Follow directions,
Respond accurately,
Submit the assignment [one page, typed; no email] on or
before the due date.
You should use both the site to which you are directed and your text.
PLEASE NOTE - your specific task is listed by
Class [so, jr, sen] AND Major may be an option
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All SOPHOMORES [or less than 15hr Chem/Biol] regardless of major -
Access the following site on the web:
http://www.rcsb.org/pdb/molecules/pdb18_1.html
Your focus for this exercise is myosin.
Respond to the following.
Link to sites [listed on this page] as needed.
All links are on the above web page or on continuation pages.
1] What is the Protein Data Bank? (use PDB Home link)
2] Go BACK to the original page on myosin.
In the paragraph on Molecular Motion, the author relates
myosin's main role in the body and gives examples. Your task -
Distinguish between voluntary muscles and involuntary muscles.
3] link to "Sprinting with Myosin" - what are the 3 sources of
organic molecules used for energy described in this paragraph? Which
molecule is used over sustained exercise? Does this agree with your text?
4] Compare the diagrams of myosin in your text with the one on the
myosin web page and the image seen by clicking on "Power in Numbers".
What is important about the motor domain?
How many myosin molecules are required to provide the force necessary to
hold a ball?
5] Click forward to the frame - "Exploring the Structure"
Briefly describe the motor domain.
6] Read the excerpt below from the web page of
Christopher P. Ingalls, Department of Kinesiology and Health,
Georgia State University
Our research on exercise-induced muscle injury indicates that
excitation-contraction uncoupling is the primary mechanism responsible for
strength deficits occurring early after injury induction (i.e.,
immediately after to 5 days), whereas frank loss of contractile protein is
the primary mechanism at later time points (i.e., 14 to 28 days). Our
research on unloading-induced muscle atrophy suggests that
excitation-contraction uncoupling does not contribute to strength
reductions in the mouse soleus muscle after two weeks of hindlimb
suspension.
Answer the 2 ?s below
What is muscle atrophy?
Why would you expect that long term injury requires a longer period of
recovery?
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SENIORS - Chem, Biol, Micro majors:
1]Access - http://www.hhmi.org/news/goldstein2.html
Summarize the short article. What is the role of transport proteins and
why are they implicated in dementia?
2] Go to the Protein Data Bank. http://www.rcsb.org/pdb/index.html
Search EACH of the following proteins and answer these questions.
A] Amyloid - in entries 2-4, what molecular classification is given?
Pick one of these entries. Click on EXPLORE.
Give the complete citation.
Click on View structure [left-hand column] then
click on VRML to see the protein.
Rotate the image to view the B-sheets and A- helices, etc.
B] Amyloid precursor protein - select the 1st entry to
EXPLORE and repeat all of the above
C] Kinesin - select the 1st entry to EXPLORE and repeat
all of the above
What repetitive features are seen in these proteins?
Construct a flow chart to address EITHER
the interactions of the proteins, described in the article, within the
cell under normal or Altzeimer conditions
OR
the flow of genetic information, inferred from the mutants, to the
abnormal interactions of the proteins in the Altseimer condition
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JUNIORS - all majors and SENIORS with majors not listed above.
1] Access http://www.ncbi.nlm.nih.gov/disease/DMD.html
Summarize: What is DMD? What is the normal function of dystrophin?
2] Read the excerpt below. Does the information in this abstract agree
with what you learned from the NIH site above? What information does it
add to the role of myosin?
Albrecht DE, Froehner SC. Syntrophins and dystrobrevins: defining the
dystrophin scaffold at synapses. Neurosignals 2002 May-Jun;11(3):123-9
Abstract:
Dystrophin and its associated proteins were originally identified in
skeletal muscle, where the complex provides mechanical stabilization to
the sarcolemma during contraction. However, the dystrophin complex is also
present at membrane specializations in many non-muscle cells, including
synaptic sites in neurons. The function of the dystrophin complex at these
sites is still unknown, but emerging results suggest that the dystrophin
complex can function as a scaffold for signaling proteins. In this review,
we examine the growing body of evidence that suggests the dystrophin
complex may have a dual function: membrane stabilization and transmembrane
signaling.
3] Access-
http://www.rcsb.org/pdb/index.html
In the search box, tpye in 1DXX.
From the citation, what does this molecule bind?
Click on View structure [left-hand column] then click on VRML to see the
protein.
Below is a selection from the abstract of the cited article.
Dystrophin is an essential component of skeletal muscle cells. Its
N-terminal domain binds to F-actin and its C terminus binds to the
dystrophin-associated glycoprotein (DAG) complex in the membrane.
Dystrophin is therefore thought to serve as a link from the actin-based
cytoskeleton of the muscle cell through the plasma membrane to the
extracellular matrix. Pathogenic mutations in dystrophin result in
Duchenne or Becker muscular dystrophy... Examining the position of three
pathogenic …mutations within the structure suggests that they exert their
effects through misfolding of the actin-binding region.
What other muscle proteins bind actin?
Note that proteins in both healthy and abnormal situations may have
multiple functions.
These articles claim what 2 actions for dystrophin?