Recombinant Human GGA3 protein

GGA3 (Golgi-associated, gamma adaptin ear-containing, ARF-binding protein 3) is a member of the GGA family of vesicular trafficking proteins, which play critical roles in intracellular protein sorting between the Golgi apparatus and endosomes. These proteins facilitate the selective transport of cargo molecules, such as transmembrane receptors and hydrolases, by linking clathrin-coated vesicle formation with cargo recognition. GGA proteins, including GGA1. GGA2. and GGA3. share a conserved modular structure: an N-terminal VHS domain for cargo binding, a GAT domain that interacts with ARF GTPases and ubiquitin, a hinge region recruiting clathrin and accessory proteins, and a C-terminal GAE domain involved in interactions with trafficking regulators.

Recombinant GGA3 proteins are engineered to study its structure-function relationships, post-translational modifications, and interactions with molecular partners. Researchers commonly express GGA3 fragments or full-length versions in bacterial (e.g., E. coli) or eukaryotic systems, often fused with affinity tags (e.g., His, GST) for purification. These tools enable in vitro binding assays, crystallographic studies, and functional analyses of domains like the VHS domain's recognition of sorting signals (e.g., DXXLL motifs in cargo proteins) or the GAT domain's ARF-binding capacity.

GGA3 dysregulation has been implicated in neurodegenerative diseases (e.g., altered BACE1 trafficking in Alzheimer's) and cancer (e.g., EGFR recycling modulation). Recombinant GGA3 aids in deciphering its phosphorylation-dependent regulation, ubiquitination-mediated sorting, and cross-talk with other adaptors like AP-1. Recent studies also explore its role in stress responses and lysosomal biogenesis, highlighting its therapeutic relevance. The development of mutant variants (e.g., disrupted ARF-binding sites) further clarifies mechanistic contributions to membrane trafficking pathways.