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Cited by 158Cellular transport and secretionUbiquitin and proteasome pathwaysProtein Structure and Dynamics

Epsin 1 Undergoes Nucleocytosolic Shuttling and Its Eps15 Interactor Nh2-Terminal Homology (Enth) Domain, Structurally Similar to Armadillo and Heat Repeats, Interacts with the Transcription Factor Promyelocytic Leukemia Zn2+ Finger Protein (Plzf)

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Hyman, Joel, Chen, Hong, Di Fiore, Pier Paolo, De Camilli, Pietro, Brunger, Axel T.·2000·The Journal of Cell Biology
DOI 10.1083/jcb.149.3.537PMC PMC2174850
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Abstract

Epsin (Eps15 interactor) is a cytosolic protein involved in clathrin-mediated endocytosis via its direct interactions with clathrin, the clathrin adaptor AP-2, and Eps15. The NH2-terminal portion of epsin contains a phylogenetically conserved module of unknown function, known as the ENTH domain (epsin NH2-terminal homology domain). We have now solved the crystal structure of rat epsin 1 ENTH domain to 1.8 Å resolution. This domain is structurally similar to armadillo and Heat repeats of β-catenin and karyopherin-β, respectively. We have also identified and characterized the interaction of epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn2+ finger protein (PLZF). Leptomycin B, an antifungal antibiotic, which inhibits the Crm1- dependent nuclear export pathway, induces an accumulation of epsin 1 in the nucleus. These findings suggest that epsin 1 may function in a signaling pathway connecting the endocytic machinery to the regulation of nuclear function.

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  • The first alpha helix (α0) of the N-terminal ENTH domain can insert into the membrane and induce curvature formation.

    “In addition, the first alpha helix (α0) of the N-terminal ENTH domain can insert into the membrane and induce curvature formation (Fig. 4a)89,90 – this function of Epsin1 is thought to be important for endocytosis.”

    From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [89]

    The Results section, “General Features of the Structure” (page unavailable), describes the ENTH domain’s helices but does not identify an α0 helix or report membrane insertion or curvature formation. The Introduction says the ENTH domain’s function was unknown; searches for membrane insertion and curvature found no passage addressing the claimed mechanism. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Authors
Hyman, J., Chen, H., Di Fiore, P. P., De Camilli, P., & Brunger, A. T.
Affiliations
  • Howard Hughes Medical Institute (US)
  • dDepartment of Experimental Oncology, European Institute of Oncology, Milan, Italy
  • bDepartment of Cell Biology, Yale University, New Haven, Connecticut 06520
  • aDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520
ORCID
Chen, Hong
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2000-05-01
Volume
149
Issue
3
Pages
537-546
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.149.3.537
PMC
PMC2174850
OpenAlex
W2143975798
Cited by
158
References
2
Citations by year
2025: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 5 · 2013: 7 · 2012: 7
FWCI
7.72
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • U.S. Department of Energy
  • Yale University
  • National Institutes of Health (CA-46128)
  • National Cancer Institute (P01CA046128, CA46128)
  • National Institute of Neurological Disorders and Stroke (NS36252)
  • National Center for Research Resources
  • Biological and Environmental Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
ENTH domain, armadillo repeats, HEAT repeats, crystal structure, PLZF, clathrin-mediated endocytosis, leptomycin B, transcription factor regulation, nuclear accumulation
MeSH terms
Amino Acid Sequence, Animals, Calcium-Binding Proteins, Carrier Proteins, Cell Line, Cell Nucleus, Cytoskeletal Proteins, Cytosol, DNA-Binding Proteins, Fluorescent Antibody Technique, Models, Molecular, Molecular Sequence Data, Neuropeptides, Phosphoproteins, Protein Binding, Transcription Factors, Trans-Activators, Zinc Fingers, Sequence Alignment, Crystallography, X-Ray, Insect Proteins, Drosophila Proteins, Vesicular Transport Proteins, Adaptor Proteins, Vesicular Transport, beta Catenin, Armadillo Domain Proteins, Rats

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