Solution structure of human GABA(A) receptor-associated protein GABARAP: implications for biolgoical funcrion and its regulation.
Control of neurotransmitter receptor expression and delivery to the postsynaptic membrane is of critical importance for neural signal transduction at synapses. The gamma-aminobutyric acid, type A (GABA(A)) receptor-associated protein GABARAP was reported to have an important role for movement and sorting of GABA(A) receptor molecules to the postsynaptic membrane. GABARAP not only binds to GABA(A) receptor gamma2-subunit but also to tubulin, gephyrin, and ULK1. We present for the first time the high resolution structure of human GABARAP determined by nuclear magnetic resonance in aqueous solution. One part of the molecule, despite being well ordered and rigid on a MHz time scale, exists in at least two different conformations that interchange with each other on a time scale slower than 25 Hz. An important feature of the solution structure is the observation that amino- and carboxyl-terminal ends of the protein directly interact with each other, which is not seen in recently reported crystal structures. The possible biological relevance of these observations for the regulation of GABARAP interactions and functions is discussed.
Stangler
Thomas
T
Institut für Molekulare Biotechnologie, Beutenbergstr. 11, 07745 Jena, Germany.
Mayr
Lorenz M
LM
Willbold
Dieter
D
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011963:Receptors, GABA-A / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C116741:GABARAP protein, human; D008869:Microtubule-Associated Proteins; D011963:Receptors, GABA-A; D013917:Thrombin