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7oxe

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Crystal structure of the KDEL receptor bound to HDEF peptide at pH 6.0

Structural highlights

7oxe is a 2 chain structure with sequence from Gallus gallus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.283Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ERD22_CHICK Required for the retention of luminal endoplasmic reticulum proteins. Determines the specificity of the luminal ER protein retention system. Also required for normal vesicular traffic through the Golgi. This receptor recognizes K-D-E-L (By similarity).

Publication Abstract from PubMed

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.

Molecular basis for pH sensing in the KDEL trafficking receptor.,Wu Z, Smith K, Gerondopoulos A, Sobajima T, Parker JL, Barr FA, Newstead S, Biggin PC Structure. 2024 Jul 11;32(7):866-877.e4. doi: 10.1016/j.str.2024.03.013. Epub , 2024 Apr 15. PMID:38626766^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu Z, Smith K, Gerondopoulos A, Sobajima T, Parker JL, Barr FA, Newstead S, Biggin PC. Molecular basis for pH sensing in the KDEL trafficking receptor. Structure. 2024 Jul 11;32(7):866-877.e4. PMID:38626766 doi:10.1016/j.str.2024.03.013