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| Subject Categories: Structural Biology | Membranes & Transport |
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| The EMBO Journal
(2004) 23, 4371–4383, doi:10.1038/sj.emboj.7600445 Published online 21 October 2004 |
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Evolving nature of the AP2  -appendage hub during clathrin-coated vesicle endocytosis |
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| Gerrit J K Praefcke1, 2, Marijn G J Ford1, Eva M Schmid, Lene E Olesen, Jennifer L Gallop, Sew-Yeu Peak-Chew, Yvonne Vallis, M Madan Babu, Ian G Mills3 and Harvey T McMahon |
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Medical Research Council Laboratory of Molecular Biology, Cambridge, UK To whom correspondence should be addressed Harvey T McMahon, Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 2QH, UK. Tel.: +44 1223 402311; Fax: +44 1223 402310; E-mail: hmm@mrc-lmb.cam.ac.uk 1 These authors contributed equally to this work 2 Present address: Zentrum für Molekulare Medizin der Universität Köln, Institut für Genetik, Zülpicher Stra  e 47, 50674 Köln, Germany3 Present address: The Oncology Department, University of Cambridge Hutchison/MRC Cancer Research Centre, Cambridge CB2 2XZ, UK Received 18 August 2004; Accepted 21 September 2004; Published online 21 October 2004. |
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| Abstract |
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| Clathrin-mediated endocytosis involves the assembly of a network of proteins that select cargo, modify membrane shape and drive invagination, vesicle scission and uncoating. This network is initially assembled around adaptor protein (AP) appendage domains, which are protein interaction hubs. Using crystallography, we show that FxDxF and WVxF peptide motifs from synaptojanin bind to distinct subdomains on -appendages, called 'top' and 'side' sites. Appendages use both these sites to interact with their binding partners in vitro and in vivo. Occupation of both sites simultaneously results in high-affinity reversible interactions with lone appendages (e.g. eps15 and epsin1). Proteins with multiple copies of only one type of motif bind multiple appendages and so will aid adaptor clustering. These clustered (appendage)-hubs have altered properties where they can sample many different binding partners, which in turn can interact with each other and indirectly with clathrin. In the final coated vesicle, most appendage binding partners are absent and thus the functional status of the appendage domain as an interaction hub is temporal and transitory giving directionality to vesicle assembly. |
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| Keywords: AP180, clathrin-AP2 adaptors, eps15, epsin1, synaptojanin |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSThe long and short of adaptor appendages Nature Structural Biology News and Views (01 Aug 2003) Ephrin tempers two-faced synaptojanin 1 Nature Cell Biology News and Views (01 May 2005) RESEARCHEngineering Oncolytic Measles Virus to Circumvent the Intracellular Innate Immune Response Molecular Therapy Original Article The NECAP PHear domain increases clathrin accessory protein binding potential The EMBO Journal Article (19 Sep 2007) |
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