7M1Q

Human ABCA4 structure in complex with N-ret-PE

7M1Q の概要

• エントリーDOI: 10.2210/pdb7m1q/pdb
• EMDBエントリー: 23618
• 分子名称: Retinal-specific phospholipid-transporting ATPase ABCA4, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: abc transporter, importer, membrane protein, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 260061.90

構造登録者

Scortecci, J.F.,Van Petegem, F.,Molday, R.S. (登録日: 2021-03-14, 公開日: 2021-09-08, 最終更新日: 2024-11-06)

主引用文献

Scortecci, J.F.,Molday, L.L.,Curtis, S.B.,Garces, F.A.,Panwar, P.,Van Petegem, F.,Molday, R.S.
Cryo-EM structures of the ABCA4 importer reveal mechanisms underlying substrate binding and Stargardt disease.
Nat Commun, 12:5902-5902, 2021

PubMed Abstract: ABCA4 is an ATP-binding cassette (ABC) transporter that flips N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leaflet of photoreceptor membranes. Loss-of-function mutations cause Stargardt disease (STGD1), a macular dystrophy associated with severe vision loss. To define the mechanisms underlying substrate binding and STGD1, we determine the cryo-EM structure of ABCA4 in its substrate-free and bound states. The two structures are similar and delineate an elongated protein with the two transmembrane domains (TMD) forming an outward facing conformation, extended and twisted exocytoplasmic domains (ECD), and closely opposed nucleotide binding domains. N-Ret-PE is wedged between the two TMDs and a loop from ECD1 within the lumen leaflet consistent with a lateral access mechanism and is stabilized through hydrophobic and ionic interactions with residues from the TMDs and ECDs. Our studies provide a framework for further elucidating the molecular mechanism associated with lipid transport and disease and developing promising disease interventions.

PubMed: 34625547
DOI: 10.1038/s41467-021-26161-7

実験手法

ELECTRON MICROSCOPY (2.92 Å)