8APY

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

Summary for 8APY

• Entry DOI: 10.2210/pdb8apy/pdb
• Descriptor: ER lumen protein-retaining receptor 2, Synthetic nanobody, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (4 entities in total)
• Functional Keywords: trafficking receptor, synthetic binder, kdelr, membrane protein
• Biological source: Gallus gallus (chicken); More
• Total number of polymer chains: 2
• Total formula weight: 38377.47

Authors

Parker, J.L.,Smith, K.,Newstead, S. (deposition date: 2022-08-10, release date: 2023-08-23, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.34 Å)