Transcript excercise 1b

26-27 Oct
2009
Structure and Function
of Proteins
Winter 2009/2010
Lecturer: Dr. Ora Furman
Teaching Assistants:
Sivan Pearl
Miriam Oxsman
The HLA System
(i)
HLA: Human Leukocyte Antigen
 This human version of MHC molecules presents
pathogen-derived peptides to T-cells.
 Immune HLA genes:

o Class I (HLA-A/B/C)
• Expressed by most somatic cells.
• Used for cell-to-T-cells communication.
o 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).
The HLA System

(ii)
HLA genes are extremely polymorphic.
HLA-I allele*
# of different proteins
HLA-A
681
HLA-B
1165
HLA-C
431
* Adopted from: http://www.ebi.ac.uk/imgt/hla/stats.html

Class I and II differ in structure and function.
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
(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).
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).
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)].
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.