Binding of a Nonapeptide by MHC class I and the TCR Receptor

The structure at the right shows an MHC class I  molecule alpha chain in dark blue. The beta-2 microglobulin chain of the MHC is light blue.  The TCR receptor alpha chain is in  green and the beta chain is in dark yellow.  Held between them is a nonapeptide (9 amino acids) from the Tax protein of human T-cell lymphotropic virus -1 (HTLV-1). This is at present  in green.

Highlight the MHC class I alpha chain [Ribbons Backbone Strands   Wireframe  ]

Highlight the MHC beta-2 microglobulin chain  [Ribbons Backbone Strands   Wireframe  ]

Highlight the T cell receptor alpha chain   [Ribbons Backbone Strands   Wireframe  ]

Highlight the T cell receptor beta chain [Ribbons Backbone Strands   Wireframe  ]

Let's restore the wireframe

Now highlight the viral peptide. This is best done in space-fill . 

You can see that the peptide is held in a pocket between the MHC I alpha chain and the two chains of the T cell receptor.

Now turn off the T cell receptor

Zoom the MHC class I alpha chain and the beta-2 microglobulin .

Let's look at the interaction of the MHC class I protein with this peptide. In contrast to the situation that we shall see with the class II MHC-peptide interaction,  the conserved hydrogen bonds formed between the peptide and the MHC protein are located at the ends of the peptide. Highlight the amino acids of the MHC that interact with the N-terminus of the peptide ; highlight the amino acids that interact with the C-terminus of the peptide

Let's look at the peptide-binding pocket in the MHC I alpha chain in more detail. We can see the structure better if we change the color of the alpha chain to reveal the alpha helices in purple and the beta sheets in orange. Random coil is in gray. At the same time we will turn off the highlighted hydrogen-binding amino acids . You can see that the pocket that holds the peptide has alpha helical walls and a floor of beta sheet.

Polymorphism analyses of the amino acid sequences show that regions of high variability are restricted to the amino terminal domain of the alpha chain, the part of the molecule that is involved in the peptide binding pocket. The amino terminal domain of the alpha chain is made up of the alpha1 , alpha 2 and alpha 3 regions of the protein. 

Now reset the helices and sheets

In fact, the highly variable residues are specifically clustered around the  floor or the walls of the pocket. Highlight the highly variable residues here . You can see how the variable residues are clustered around the peptide-binding pocket by rotating the molecule .  Now convert the display to strands , zoom out   and rotate   

The molecule can be rotated at any time by left clicking the mouse on the molecule and dragging the image with the left button depressed or you can switch on rotation here: Rotate On    Rotate Off   

You can also zoom in on your changes here [ Zoom 150%   Zoom 200% Zoom 300%   Reset Zoom   Rotate On Rotate Off ]. The zoom defaults to the center of the molecule. Hold down the control key to drag the molecule to the position that you want with the right mouse button.

The protein database file is here   Get Chime here