Prof. Cesare Indiveri
Unit of Biochemistry & Molecular Biotechnology
Department DiBEST
Università della Calabria
Website
Programm
"The intriguing SLC7A5 amino acid transporter: structure/function relationships, regulation and relevance to human health"
SLC7A5, also known as LAT1, is a transporter for essential amino acids located at the Blood Brain Barrier and Placenta Barrier and is over-expressed in human cancers. LAT1 forms a functional heterodimer with the glycoprotein SLC3A2, responsible for the trafficking to the plasma membrane. The transport cycle of LAT1 has been described by computational analyses using the available 3D structures and some homology models. The binding constants derived from docking analyses depend on the conformation of the protein, indicating that the affinity of substrates is mostly determined by the occluded conformations. ATP and cholesterol synergistically stimulate the transport function acting on the rate of transport. Intriguingly, under specific conditions, LAT1 mediates an ATP-dependent uniport of the substrate His in complex with Cu2+. This apparently unphysiological function explains the efficacy of the Cu-(His)2 administration in the treatment of Menkes Disease patients. In this respect, the LAT1 mediated transport of Cu-(His)2 can be exploited for the treatment of human cancers.
Host: Sonja SUCIC
Contact for questions: Helmut KUBISTA