Crystal structure of the amphiphysin‐2 SH3 domain and its role in the prevention of dynamin ring formation
Open accessAbstract
The amphiphysins are brain-enriched proteins, implicated in clathrin-mediated endocytosis, that interact with dynamin through their SH3 domains. To elucidate the nature of this interaction, we have solved the crystal structure of the amphiphysin-2 (Amph2) SH3 domain to 2.2 A. The structure possesses several notable features, including an extensive patch of negative electrostatic potential covering a large portion of its dynamin binding site. This patch accounts for the specific requirement of amphiphysin for two arginines in the proline-rich binding motif to which it binds on dynamin. We demonstrate that the interaction of dynamin with amphiphysin SH3 domains, unlike that with SH3 domains of Grb2 or spectrin, prevents dynamin self-assembly into rings. Deletion of a unique insert in the n-Src loop of Amph2 SH3, a loop adjacent to the dynamin binding site, significantly reduces this effect. Conversely, replacing the n-Src loop of the N-terminal SH3 domain of Grb2 with that of Amph2 causes it to favour dynamin ring disassembly. Transferrin uptake assays show that shortening the n-Src loop of Amph2 SH3 reduces the ability of this domain to inhibit endocytosis in vivo. Our data suggest that amphiphysin SH3 domains are important regulators of the multimerization cycle of dynamin in endocytosis.
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The BIN1 CLAP domain is critical to recruiting dynamin and regulating its self-assembly at the clathrin-coated pit.
“Crystal structure and functional studies predicted that the BIN1 CLAP domain is critical to recruiting dynamin and regulate its self-assembly at the clathrin-coated pit [15].”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [15]
The Introduction identifies amphiphysin-2 as BIN1 and says its SH3 domain interacts with dynamin. In “Control of dynamin ring assembly by the amphiphysins,” the authors propose that amphiphysin helps recruit dynamin to coated pits and report that its SH3 domains affect dynamin ring assembly. The paper does not assign those roles to a BIN1 CLAP domain, and recruitment is presented as a proposed role rather than an established necessity. (LLM, conf=0.89)
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Cites
Butler, M. H., David, C., Ochoa, G.-C., Freyberg, Z., Daniell, L., Grabs, D., Cremona, O., & Camilli, P. D. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.6.1355 · Cited by 256 · see citing works
SH3 domain‐dependent interactions of endophilin with amphiphysin
(1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01016-8 · Cited by 91 · see citing works
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Research works printed but not linked: 3
- David,C., McPherson,P.S., Mundigl,O. and DeCamilli,P. (1996) A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals. Proc. Natl Acad. Sci. USA, 93, 331-335.
- Ringstad,N., Nemoto,Y. and DeCamilli,P. (1997) The SH3p4/SH3p8/ SH3p13 protein family: Binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain. Proc. Natl Acad. Sci. USA, 94, 8569-8574.
- Sheldrick,G.M. (1991) In Wolf,W., Evans,P.R. and Leslie,A.G.W. (eds), Heavy Atom Location Using SHELXS-90. SERC, Daresbury Laboratory, Warrington, UK, pp. 23-38.
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Nicot, A.-S., Toussaint, A., Tosch, V., Kretz, C., Wallgren-Pettersson, C., Iwarsson, E., Kingston, H., Garnier, J.-M., Biancalana, V., Oldfors, A., et al. (2007) · Nature Genetics · doi:10.1038/ng2086 · Cited by 434 · see citing works
Meinecke, M., Boucrot, E., Camdere, G., Hon, W.-C., Mittal, R., & McMahon, H. T. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.444869 · Cited by 155 · see citing works
Self-citationDe Rossi, P., Buggia-Prévot, V., Clayton, B. L. L., Vasquez, J. B., van Sanford, C., Andrew, R. J., Lesnick, R., Botté, A., Deyts, C., Salem, S., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0124-1 · Cited by 151 · see citing works
“Crystal structure and functional studies predicted that the BIN1 CLAP domain is critical to recruiting dynamin and regulate its self-assembly at the clathrin-coated pit [15].”
Dergai, M., Tsyba, L., Dergai, O., Zlatskii, I., Skrypkina, I., Kovalenko, V., & Rynditch, A. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.07.080 · Cited by 35 · see citing works
- Authors
- Owen, D. J., Wigge, P., Vallis, Y., Moore, J. D. A., Evans, P. R., & McMahon, H. T.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Venue
- The EMBO Journal
- Published
- 1998-09-15
- Volume
- 17
- Issue
- 18
- Pages
- 5273-5285
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170855
- OpenAlex
- W2143369277
- Cited by
- 171
- References
- 2
- Citations by year
- 2025: 5 · 2024: 7 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 7 · 2015: 3 · 2014: 4 · 2013: 6 · 2012: 5
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- SH3 domain, dynamin, clathrin-mediated endocytosis, protein-protein interaction, electrostatic potential, Grb2, transferrin uptake
- MeSH terms
- Amino Acid Sequence, Animals, Endocytosis, Fibroblasts, Models, Molecular, Molecular Sequence Data, Nerve Tissue Proteins, Protein Conformation, Proteins, Transferrin, Point Mutation, Crystallography, X-Ray, src Homology Domains, GTP Phosphohydrolases, Dynamins, Adaptor Proteins, Signal Transducing, GRB2 Adaptor Protein, Rats
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