Article
- The EMBO Journal (2005) 24, 261 - 269
- doi:10.1038/sj.emboj.7600529
Published online: 23 December 2004
Subject Categories:
Structural insights into the EB1–APC interaction
Srinivas Honnappa1,a, Corinne M John1,2,a, Dirk Kostrewa1, Fritz K Winkler1 and Michel O Steinmetz1
- Biomolecular Research, Structural Biology, Paul Scherrer Institut, Villigen PSI, Switzerland
- Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), Zürich, Switzerland
Correspondence to:
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
aThese authors contributed equally to this work
Received 22 September 2004; Accepted 30 November 2004
Abstract
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.
Keywords:
- coiled coil,
- microtubule plus-end tracking proteins,
- phosphorylation,
- protein–protein interaction,
- +TIP
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