ZAP70: Domains

Src Homology 2 Domain
Protein Tyrosine Kinase Domain

Src Homology 2 Domain (SH2)

Conserved domain within the Src oncology family.
110-110 amino acids in length
Mr = 12KDa
Functions as an intracellular signal transducer
2 tandem SH2 domains work congruently, joined together by a linker called 'interdomain A', within ZAP70 in order to recruit the protein to the inter-membrane T-cell receptor. This consequently correctly orientates ZAP70 for the subsequent mechanisms within the signalling pathway.

A central antiparallel β sheet with a single α helix either side with one or more loops make up the 'sockets' of this domain, which enables binding to complimentary 'plugs' on the phosphorylated 4 ITAM domains on the 2 CD3-zeta chains. Socket 1 specifically recognises the phosphorylated tyrosine residues within the ITAM domain and socket 2 has a selective amino acid lining of both charged and hydrophobic residues which allows the specificity of which peptide can bind to the pocket according to the third amino acid, upstream of the phosphorylated tyrosine in the ITAM domain. This is called the 'plug and socket' model.

Protein Tyrosine Kinase Domain

Conserved domain within the protein kinase family
Catalytically functions to chemically modify proteins by phosphorylation of tyrosine residues once it has itself been phosphorylated for full catalytic activity. This induces a conformational change thereby switching the phosphorylated protein 'on'.
The kinase is separated into 2 lobes of differing conserved protein folding motifs with a linker between which determines the location of the ATP molecule.
Within the catalytic loop of the domain, phosphorylation of tyrosine (Y) 492 has a negative regulatory role whereas Y493 has a positive regulatory role on the activity of the kinase active site. The interplay of this ensures controlled signal transduction.
This domain is linked to the second SH2 domain within ZAP70 by a linker called inter-domain B