3N6V

Structure of the GluA2 NTD-dimer interface mutant, T78A

3N6V の概要

• エントリーDOI: 10.2210/pdb3n6v/pdb
• 関連するPDBエントリー: 3HSY 3O2J
• 分子名称: Glutamate receptor 2 (2 entities in total)
• 機能のキーワード: ampa, assembly, ntd, glur2, glua2, transport protein
• 由来する生物種: Rattus norvegicus (rat)
• 細胞内の位置: Cell membrane; Multi-pass membrane protein: P19491
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 253702.78

構造登録者

Rossmann, M.,Sukumaran, M.,Greger, I.H. (登録日: 2010-05-26, 公開日: 2011-03-09, 最終更新日: 2024-11-20)

主引用文献

Rossmann, M.,Sukumaran, M.,Penn, A.C.,Veprintsev, D.B.,Babu, M.M.,Greger, I.H.
Subunit-selective N-terminal domain associations organize the formation of AMPA receptor heteromers
Embo J., 30:959-971, 2011

PubMed Abstract: The assembly of AMPA-type glutamate receptors (AMPARs) into distinct ion channel tetramers ultimately governs the nature of information transfer at excitatory synapses. How cells regulate the formation of diverse homo- and heteromeric AMPARs is unknown. Using a sensitive biophysical approach, we show that the extracellular, membrane-distal AMPAR N-terminal domains (NTDs) orchestrate selective routes of heteromeric assembly via a surprisingly wide spectrum of subunit-specific association affinities. Heteromerization is dominant, occurs at the level of the dimer, and results in a preferential incorporation of the functionally critical GluA2 subunit. Using a combination of structure-guided mutagenesis and electrophysiology, we further map evolutionarily variable hotspots in the NTD dimer interface, which modulate heteromerization capacity. This 'flexibility' of the NTD not only explains why heteromers predominate but also how GluA2-lacking, Ca(2+)-permeable homomers could form, which are induced under specific physiological and pathological conditions. Our findings reveal that distinct NTD properties set the stage for the biogenesis of functionally diverse pools of homo- and heteromeric AMPAR tetramers.

PubMed: 21317873
DOI: 10.1038/emboj.2011.16

実験手法

X-RAY DIFFRACTION (3.2 Å)