8APY

Crystal structure of the H12A variant of the KDEL receptor bound to sybody

8APY の概要

• エントリーDOI: 10.2210/pdb8apy/pdb
• 分子名称: ER lumen protein-retaining receptor 2, Synthetic nanobody, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (4 entities in total)
• 機能のキーワード: trafficking receptor, synthetic binder, kdelr, membrane protein
• 由来する生物種: Gallus gallus (chicken); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38377.47

構造登録者

Parker, J.L.,Smith, K.,Newstead, S. (登録日: 2022-08-10, 公開日: 2023-08-23, 最終更新日: 2024-11-06)

主引用文献

Wu, Z.,Smith, K.,Gerondopoulos, A.,Sobajima, T.,Parker, J.L.,Barr, F.A.,Newstead, S.,Biggin, P.C.
Molecular basis for pH sensing in the KDEL trafficking receptor.
Structure, 32:866-877.e4, 2024

PubMed Abstract: Trafficking receptors control protein localization through the recognition of specific signal sequences that specify unique cellular locations. Differences in luminal pH are important for the vectorial trafficking of cargo receptors. The KDEL receptor is responsible for maintaining the integrity of the ER by retrieving luminally localized folding chaperones in a pH-dependent mechanism. Structural studies have revealed the end states of KDEL receptor activation and the mechanism of selective cargo binding. However, precisely how the KDEL receptor responds to changes in luminal pH remains unclear. To explain the mechanism of pH sensing, we combine analysis of X-ray crystal structures of the KDEL receptor at neutral and acidic pH with advanced computational methods and cell-based assays. We show a critical role for ordered water molecules that allows us to infer a direct connection between protonation in different cellular compartments and the consequent changes in the affinity of the receptor for cargo.

PubMed: 38626766
DOI: 10.1016/j.str.2024.03.013

実験手法

X-RAY DIFFRACTION (2.34 Å)