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Structure and Function of Proteins

26-27 Oct 2009. Teaching Assistants:. Sivan Pearl Miriam Oxsman. Structure and Function of Proteins. Winter 2009/2010. Lecturer: Dr. Ora Furman. The HLA System (i). HLA: Human Leukocyte Antigen This human version of MHC molecules presents pathogen-derived peptides to T-cells.

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Structure and Function of Proteins

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  1. 26-27 Oct 2009 Teaching Assistants: Sivan Pearl Miriam Oxsman Structure and Function of Proteins Winter 2009/2010 Lecturer: Dr. Ora Furman

  2. The HLA System (i) • HLA: Human Leukocyte Antigen • This human version of MHC molecules presents pathogen-derived peptides to T-cells. • Immune HLA genes: • Class I (HLA-A/B/C) • Expressed by most somatic cells. • Used for cell-to-T-cells communication. • Class II (HLA-D) • Expressed by B-cells, activated T-cells, MΦ, DCs and thymic endothelium. • Used for communication among cells of the immune system (T-helper cells stimulation).

  3. The HLA System(ii) • HLA genes are extremely polymorphic. • Class I and II differ in structure and function. * Adopted from:http://www.ebi.ac.uk/imgt/hla/stats.html

  4. The HLA System(iii) Class I vs. class II structure: Adopted from: Klein et. al, N Engl J Med. (2000);343(10):702-9.

  5. The HLA System(iv) HLA-peptide interactions: • Class I groove accommodates 7 to 15 residues long peptides. • An HLA class I molecule has 6 pockets along the groove, 2 or 3 determine peptide specificity. • Particular allele product binds thousands of ligands. Adopted from: Klein et. al, N Engl J Med. (2000);343(10):702-9. (fig. 5).

  6. Superimposition One molecule is rotated and translated to fit the other with minimal RMS RMS =Root Mean Square (of the distances between the atoms) Adopted from: Klein et. al, N Engl J Med. (2000);343(10):702-9. (fig. 5).

  7. Homework I SUBMIT IN PAIRS ! Question 1 Please send the figure by email to Sivan • Question 2 • Rehearse some basic facts that regard interactions. You can look at the introductions of the course’ books (see course’ website for the booklist). • Look at the presentation from the 1st lesson and try to think of all possible AA-AA interactions [Hydrophobic, ionic and H-bonds (disregard donor/acceptor issues)].

  8. Homework II • Question 2 – cont. • Use PDB and sPDBv to find the neighbors of positions 2 and 9 in both molecules. • Elaborate on the way in which a certain trait of the peptide’s AA might effect its neighbors’ identity: compare the neighbors of position 2 in the 1st molecule to the neighbors of position 2 in the 2nd; the same for position 9.

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