Structure and Function of Proteins

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Structure and Function of Proteins
26-27 Oct 2009
Winter 2009/2010

• Lecturer Dr. Ora Furman

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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, MF, DCs
  and thymic endothelium.
• Used for communication among cells of the immune
  system (T-helper cells stimulation).

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The HLA System (ii)

• HLA genes are extremely polymorphic.
• Class I and II differ in structure and function.

of different proteins HLA-I allele
681 HLA-A
1165 HLA-B
431 HLA-C
Adopted from http//www.ebi.ac.uk/imgt/hla/sta
ts.html
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The HLA System (iii)
Class I vs. class II structure
Adopted from Klein et. al, N Engl J Med.
(2000)343(10)702-9.
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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).
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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).
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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).

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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 peptides 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.