Abstract
Many eukaryiotic proteins are glycosylated after translation to become mature proteins. Efficient sorting of such glycosylated proteins is essential for the cell's function and is achieved by vesicle transport. Mannose 6-phosphate (M6P) modification of lysosomal proteins is recognized by a M6P receptor (MPR) which incorporates the lysosomal proteins to vesicles. Recently GGA proteins have been identified and later verified as a new family of adapter proteins distinct from well known AP-1 to 4 complexes. They are responsible for vesicle transport of glycosylated human proteins from the Golgi apparatus to early endosomesl lysosomes. We have determined the crystal structures of the VHS domain of human GGA 1 and the ear domain of human γ1 adaptin. Combined with biochemical and cell-biological data, these structures reveal the recognition mechanisms of the acidic dileucine motif signal of mannose-6-phophate receptor by the VHS domain of human GGA protein and the interaction between the ear domain of γ1 adaptin of the AP-1 complex and γ-synergin and Rabaptin-5. They constitute part of a rapidly growing ensemble of structures of transport proteins, where protein-protein interactions, as elucidated by X-ray structural analyses, play critical roles.
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