Struktuelle Untersuchungen an membranassoziierten Proteinen

The transmembrane glycoprotein CD4 (cluster determinant 4) plays a prominent role in
the adaptive immune response . CD4 is displayed primarily on the surface of T helper cells,
but also on subsets of memory and regulatory T lymphocytes . Binding of the lymphocyte
specific tyrosine kinase p56LcK to the cytoplasmic domain of CD4 is crucial for antigen
receptor-mediated signal transduction . The human immunodeficiency virus (HIV) utilizes
CD4 as the main receptor for T-cell invasion . The virus has developed multiple strategies
for down-regulation of CD4 in infected cells . The HIV-1 protein U (VpU) is an accessory
protein responsible for enhancement of virus particle release and downregulation of CD4.
Physical interactions of viral proteins VpU and Nef with the cytoplasmic tail of CD4
initiate a cascade of events leading to degradation of CD4 . Phosphorylation of serines 53
and 57 of VpU plays an essential role in CD4 downregulation.