6HKC

Solution structure of the Sushi 1 domain of GABAbR1a

Summary for 6HKC

• Entry DOI: 10.2210/pdb6hkc/pdb
• NMR Information: BMRB: 27581
• Descriptor: Gamma-aminobutyric acid type B receptor subunit 1 (1 entity in total)
• Functional Keywords: neurotransmitter receptor, g protein coupled receptors, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 8519.71

Authors

Volkov, A.N.,Buts, L.,Van Molle, I. (deposition date: 2018-09-06, release date: 2019-01-23, Last modification date: 2024-11-06)

Primary citation

Rice, H.C.,de Malmazet, D.,Schreurs, A.,Frere, S.,Van Molle, I.,Volkov, A.N.,Creemers, E.,Vertkin, I.,Nys, J.,Ranaivoson, F.M.,Comoletti, D.,Savas, J.N.,Remaut, H.,Balschun, D.,Wierda, K.D.,Slutsky, I.,Farrow, K.,De Strooper, B.,de Wit, J.
Secreted amyloid-beta precursor protein functions as a GABABR1a ligand to modulate synaptic transmission.
Science, 363:-, 2019

PubMed Abstract: Amyloid-β precursor protein (APP) is central to the pathogenesis of Alzheimer's disease, yet its physiological function remains unresolved. Accumulating evidence suggests that APP has a synaptic function mediated by an unidentified receptor for secreted APP (sAPP). Here we show that the sAPP extension domain directly bound the sushi 1 domain specific to the γ-aminobutyric acid type B receptor subunit 1a (GABAR1a). sAPP-GABAR1a binding suppressed synaptic transmission and enhanced short-term facilitation in mouse hippocampal synapses via inhibition of synaptic vesicle release. A 17-amino acid peptide corresponding to the GABAR1a binding region within APP suppressed in vivo spontaneous neuronal activity in the hippocampus of anesthetized Thy1-GCaMP6s mice. Our findings identify GABAR1a as a synaptic receptor for sAPP and reveal a physiological role for sAPP in regulating GABAR1a function to modulate synaptic transmission.

PubMed: 30630900
DOI: 10.1126/science.aao4827

Experimental method

SOLUTION NMR