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Bi1_2011_PS7_solution

Bi1_2011_PS7_solution - Bi1 The Biology and Biophysics of...

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Bi1: The Biology and Biophysics of Viruses Spring 2011 Problem Set 7: MHC and Cell-Mediated Immune System Due Tuesday, May 24 at 4:00 P.M. in the Bi 1 closet Name: ANSWER KEY ___________________________________________________ Section # : ___________________________________________________________ Mail Code : ___________________________________________________________ TA Names : ___________________________________________________________ Date and Time turned in : _______________________________________________ Number of pages including this one : _____________________________________ AFTER YOU FINISH: How long did it take you to complete this problem set? ____________________________ Go to the Bi1 moodle site at http://courses.caltech.edu/ and take the homework survey There are 3 questions. The number of parts to each question is listed at the beginning of each; be sure to answer all the parts! Grade: Problem 1 __________ Problem 2 __________ Problem 3 __________ TOTAL: _________ HOMEWORK INSTRUCTIONS 1) Turn in your homework stapled to this cover page. 2) Use separate sheets of paper for your answers. 3) Write or type your answers neatly. 4) Put your name on each page of your answers. 5) Box your answers, please, so that the grader can find them. Points may be deducted if you don’t follow the se instructions!
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Page 2 of 11 Recommended reading for problem set: PyMOL tutorial on the Assignment web page Chapter 49 (3/E and 2/E) The immune system in animals Chapter 3 (3/E and 2/E) Protein structure and folding Lectures 21-22 (MHC and T cells) Problem 1: MHC structure (Pymol) (30 points 3 parts) This question requires the use of Pymol and the PDB file HLA.pdb. Please refer to the Pymol Manual for assistance with the program. First, download the HLA.pdb file from the course website and open the structure in Pymol. The displayed data was obtained through X-ray crystallographic methods and depicts the human class I major histocompatibility complex, HLA- A2. The shown structure contains two chains. Familiarize yourself with the structure by coloring chain A pink (from the command line, enter ’color pink, chain A’) . This chain contains the membrane- distal polymorphic α1 and α2 domains and the relatively conserved membrane- proximal α3 domain. Color chain B blue. This smaller subunit is the conserved membrane - proximal β2 -microglobulin domain. Although the groove of a class I MHC molecule is normally occupied with a peptide, the coordinates for such a peptide are not included in the given file. A. Peptides that bind to class I MHC molecules are normally 7 to 10 residues long, spanning the entire length of the class I MHC groove without extending past either end. The structure contains two long α -helices in th e α1 and α2 domains. To accurately gauge the dimensions of a bound peptide, show the helices in a space-filling representation. To efficiently accomplish this task, color HLA by secondary structure as shown below: Display the HLA sequence (from the menu Display, choose “Sequence on” and select the residues in the first of the long helices in chain A (residues 57-85). Show your selection as spheres. Repeat the process for the second long helix (residues 138-175). Your structure should now look similar to the image below:
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Page 3 of 11 i. (3 points) Use the measurement tool (refer to the Pymol manual) to obtain a distance in Ångstroms for the approximate length of the peptide-binding groove and report this value.
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