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| Subject Categories: Structural Biology | Cell Cycle |
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| The EMBO Journal
(2005) 24, 261–269, doi:10.1038/sj.emboj.7600529 Published online 23 December 2004 |
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| Structural insights into the EB1–APC interaction |
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| Srinivas Honnappa1, 3, Corinne M John1, 2, 3, Dirk Kostrewa1, Fritz K Winkler1 and Michel O Steinmetz1 |
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1 Biomolecular Research, Structural Biology, Paul Scherrer Institut, Villigen PSI, Switzerland 2 Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), Zürich, Switzerland To whom correspondence should be addressed Michel O Steinmetz, Paul Scherrer Institut, 5232 Villigen PSI, Switzerland. Tel.: +41 56 310 4754; Fax: +41 61 310 5288; E-mail: michel.steinmetz@psi.ch 3 These authors contributed equally to this work Received 22 September 2004; Accepted 30 November 2004; Published online 23 December 2004. |
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| Abstract |
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EB1 proteins bind to microtubule ends where they act in concert with other components, including the adenomatous polyposis coli (APC) tumor suppressor, to regulate the microtubule filament system. We find that EB1 is a stable dimer with a parallel coiled coil and show that dimerization is essential for the formation of its C-terminal domain (EB1-C). The crystal structure of EB1-C reveals a highly conserved surface patch with a deep hydrophobic cavity at its center. EB1-C binds two copies of an APC-derived C-terminal peptide (C-APCp1) with equal 5  M affinity. The conserved APC Ile2805–Pro2806 sequence motif serves as an anchor for the interaction of C-APCp1 with the hydrophobic cavity of EB1-C. Phosphorylation of the conserved Cdc2 site Ser2789–Lys2792 in C-APCp1 reduces binding four-fold, indicating that the interaction APC–EB1 is post-translationally regulated in cells. Our findings provide a basis for understanding the dynamic crosstalk of EB1 proteins with their molecular targets in eukaryotic organisms. |
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| Keywords: coiled coil, microtubule plus-end tracking proteins, phosphorylation, protein–protein interaction, +TIP |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSTeaching tumour suppressors new tricks Nature Cell Biology News and Views (01 Apr 2000) RESEARCHEB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration Nature Cell Biology Article (01 Sep 2004) EB1 reveals mobile microtubule nucleation sites in Arabidopsis Nature Cell Biology Letter (01 Nov 2003) Nature Cell Biology Letter (01 Oct 2008) |
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