tailieunhanh - Báo cáo khoa học: Structural framework of the GABARAP–calreticulin interface – implications for substrate binding to endoplasmic reticulum chaperones

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a cell-autonomous process that eliminates large quantities of misfolded, newly synthesized protein, and is thus essential for the survival of any basic eukaryotic cell. | Structural framework of the GABARAP-calreticulin interface - implications for substrate binding to endoplasmic reticulum chaperones Yvonne Thielmann1 Oliver H. Weiergraber1 Jeannine Mohrluder1 2 and Dieter Willbold1 2 1 Institut fur Neurowissenschaften und Biophysik Molekulare Biophysik Forschungszentrum Julich Germany 2 Institut fur Physikalische Biologie und BMFZ Heinrich-Heine-Universitat Dusseldorf Germany Keywords 4-aminobutyrate type A receptor-associated protein GABARAP calreticulin protein-protein interaction structure model X-ray crystallography Correspondence O. H. Weiergraber Institut fur Neurowissenschaften und Biophysik Molekulare Biophysik Forschungszentrum Juulich 52425 Julich Germany Fax 49 2461 612020 Tel 49 2461 612028 E-mail D. Willbold Institut fur Physikalische Biologie und BMFZ Heinrich-Heine-Universitat 40225 Dusseldorf Germany Fax 49 2461 612023 Tel 49 2461 612100 E-mail The 4-aminobutyrate type A receptor-associated protein GABARAP is a versatile adaptor protein that plays an important role in intracellular vesicle trafficking particularly in neuronal cells. We have investigated the structural determinants underlying the interaction of GABARAP with cal-reticulin using spectroscopic and crystallographic techniques. Specifically we present the crystal structure of GABARAP in complex with its major binding epitope on the chaperone. Molecular modeling of a complex containing full-length calreticulin suggests a novel mode of substrate interaction which may have functional implications for the calreticulin calnexin family in general. Database The atomic coordinates and structure factor amplitudes code 3DOW have been deposited in the Protein Data Bank http Received 14 October 2008 revised 2 December 2008 accepted 12 December 2008 doi The neurotransmitter 4-aminobutyrate GABA mediates synaptic inhibition in the brain and the spinal cord 1 . GABA .