ArticleeLife2021
A signal capture and proofreading mechanism for the KDEL-receptor explains selectivity and dynamic range in ER retrieval.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Loss of KDEL function from a calreticulin frameshift mutation drives expression of an immature, mutant calreticulin-dependent form of the thrombopoietin receptor MPL.Haematologica · 2026Article
- Pyra-metho-carnil disrupts cancer cell proteostasis and induces apoptosis by binding to KDEL receptors.Scientific reports · 2026Article
- Endoplasmic Reticulum Redoxome: Protein Folding and Beyond.Biochemistry · 2026Review
- Towards a unified framework for the function of endoplasmic reticulum exit sites.Nature reviews. Molecular cell biology · 2025Review
- Discovery of mono-ADP ribosylating toxins with high structural homology to Pseudomonas exotoxin A.Communications biology · 2025Article
- Molecular basis for pH sensing in the KDEL trafficking receptor.Structure (London, England : 1993) · 2024Article
- Does the KDEL receptor cycle between the Golgi and the ER?Nature communications · 2024Article
- Reply to: Does the KDEL receptor cycle between the Golgi and the ER?Nature communications · 2024Article
- Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.Science (New York, N.Y.) · 2023Article
- Knock-sideways by inducible ER retrieval enables a unique approach for studyingProceedings of the National Academy of Sciences of the United States of America · 2023Article
- The therapeutic mavericks: Potent immunomodulating chaperones capable of treating human diseases.Journal of cellular and molecular medicine · 2023Review
- Yeast as a tool for membrane protein production and structure determination.FEMS yeast research · 2022Article
- FERARI and cargo adaptors coordinate cargo flow through sorting endosomes.Nature communications · 2022Article
- KDEL Receptors: Pathophysiological Functions, Therapeutic Options, and Biotechnological Opportunities.Biomedicines · 2022Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
ER proteins of widely differing abundance are retrieved from the Golgi by the KDEL-receptor. Abundant ER proteins tend to have KDEL rather than HDEL signals, whereas ADEL and DDEL are not used in most organisms. Here, we explore the mechanism of selective retrieval signal capture by the KDEL-receptor and how HDEL binds with 10-fold higher affinity than KDEL. Our results show the carboxyl-terminus of the retrieval signal moves along a ladder of arginine residues as it enters the binding pocket of the receptor. Gatekeeper residues D50 and E117 at the entrance of this pocket exclude ADEL and DDEL sequences. D50N/E117Q mutation of human KDEL-receptors changes the selectivity to ADEL and DDEL. However, further analysis of HDEL, KDEL, and RDEL-bound receptor structures shows that affinity differences are explained by interactions between the variable -4 H/K/R position of the signal and W120, rather than D50 or E117. Together, these findings explain KDEL-receptor selectivity, and how signal variants increase dynamic range to support efficient ER retrieval of low and high abundance proteins.
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