Strukturelle 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.