Structure and Function of Proteins Lecturer: Dr. Ora Furman Oct 2009 Winter 2009/2010 Teaching Assistants: Sivan Pearl Miriam Oxsman
The HLA System The HLA System (i) HLA: Human Leukocyte Antigen This human version of MHC molecules presents pathogen-derived peptides to T-cells. Immune HLA genes: oClass I (HLA-A/B/C) Expressed by most somatic cells. Used for cell-to-T-cells communication. oClass 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).
The HLA System The HLA System (ii) HLA genes are extremely polymorphic. Class I and II differ in structure and function. # of different proteinsHLA-I allele* 681HLA-A 1165HLA-B 431HLA-C * Adopted from:
The HLA System The HLA System (iii) Class I vs. class II structure: Adopted from: Klein et. al, N Engl J Med. (2000);343(10):702-9.
The HLA System The HLA System (iv) Adopted from: Klein et. al, N Engl J Med. (2000);343(10): (fig. 5). 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.
Superimposition Adopted from: Klein et. al, N Engl J Med. (2000);343(10): (fig. 5). One molecule is rotated and translated to fit the other with minimal RMS RMS = Root Mean Square (of the distances between the atoms)
Homework I Question 1 Please send the figure by 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).website Look at the presentation from the 1 st lesson and try to think of all possible AA-AA interactions [Hydrophobic, ionic and H-bonds (disregard donor/acceptor issues)]. SUBMIT IN PAIRS !
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 1 st molecule to the neighbors of position 2 in the 2 nd ; the same for position 9.