4BY4

Crystal structure of Drosophila Frq2

4BY4 の概要

• エントリーDOI: 10.2210/pdb4by4/pdb
• 関連するPDBエントリー: 4BY5
• 分子名称: FI18190P1, CALCIUM ION, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: calcium-binding protein
• 由来する生物種: DROSOPHILA MELANOGASTER (FRUIT FLY)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44108.34

構造登録者

Banos-Mateos, S.,Chaves-Sanjuan, A.,Sanchez-Barrena, M.J. (登録日: 2013-07-17, 公開日: 2014-08-13, 最終更新日: 2024-05-08)

主引用文献

Romero-Pozuelo, J.,Dason, J.S.,Mansilla, A.,Banos-Mateos, S.,Sardina, J.L.,Chaves-Sanjuan, A.,Jurado-Gomez, J.,Santana, E.,Atwood, H.L.,Hernandez-Hernandez, A.,Sanchez-Barrena, M.,Ferrus, A.
The Guanine-Exchange Factor Ric8A Binds to the Ca2+ Sensor Ncs-1 to Regulate Synapse Number and Neurotransmitter Release.
J.Cell.Sci., 127:4246-, 2014

PubMed Abstract: The conserved Ca(2+)-binding protein Frequenin (homolog of the mammalian NCS-1, neural calcium sensor) is involved in pathologies that result from abnormal synapse number and probability of neurotransmitter release per synapse. Both synaptic features are likely to be co-regulated but the intervening mechanisms remain poorly understood. We show here that Drosophila Ric8a (a homolog of mammalian synembryn, which is also known as Ric8a), a receptor-independent activator of G protein complexes, binds to Frq2 but not to the virtually identical homolog Frq1. Based on crystallographic data on Frq2 and site-directed mutagenesis on Frq1, the differential amino acids R94 and T138 account for this specificity. Human NCS-1 and Ric8a reproduce the binding and maintain the structural requirements at these key positions. Drosophila Ric8a and Gαs regulate synapse number and neurotransmitter release, and both are functionally linked to Frq2. Frq2 negatively regulates Ric8a to control synapse number. However, the regulation of neurotransmitter release by Ric8a is independent of Frq2 binding. Thus, the antagonistic regulation of these two synaptic properties shares a common pathway, Frq2-Ric8a-Gαs, which diverges downstream. These mechanisms expose the Frq2-Ric8a interacting surface as a potential pharmacological target for NCS-1-related diseases and provide key data towards the corresponding drug design.

PubMed: 25074811
DOI: 10.1242/JCS.152603

実験手法

X-RAY DIFFRACTION (2.3 Å)