Synaptic vesicle protein 2 binds adenine nucleotides.
Synaptic vesicle protein 2 (SV2) is required for normal calcium-regulated secretion of hormones and neurotransmitters. Neurons lacking the two most widely expressed isoforms, SV2A and SV2B, have a reduced readily releasable pool of synaptic vesicles, indicating that SV2 contributes to vesicle priming. The presence of putative ATP-binding sites in SV2 suggested that SV2 might be an ATP-binding protein. To explore this, we examined the binding of the photoaffinity reagent 8-azido-ATP[gamma] biotin to purified, recombinant SV2 in the presence and absence of other nucleotides. Our results indicate that SV2A and SV2B bind nucleotides, with the highest affinity for adenine-containing nucleotides. SV2A contains two binding sites located in the cytoplasmic domains preceding the first and seventh transmembrane domains. These results suggest that SV2-mediated vesicle priming could be regulated by adenine nucleotides, which might provide a link between cellular energy levels and regulated secretion.
Yao
Jia
J
Department of Pharmacology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA.
Bajjalieh
Sandra M
SM
D000225:Adenine / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D001710:Biotin / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D008861:Microsomes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D009711:Nucleotides / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry
D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009711:Nucleotides; D011994:Recombinant Proteins; C489618:Sv2a protein, rat; D001710:Biotin; D000255:Adenosine Triphosphate; D000225:Adenine