The VASP tetramerization domain is a right-handed coiled coil based on a 15-residue repeat

doi:10.1073/pnas.0403069101

The VASP tetramerization domain is a right-handed coiled coil based on a 15-residue repeat

^*Max-Planck-Institut für Molekulare Physiologie, Abteilung Strukturelle Biologie, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany; ^‡Institut für Klinische Biochemie und Pathobiochemie, Josef Schneider Strasse 2, 97080 Würzburg, Germany; ^†Max-Planck-Institut für Medizinische Forschung, Abteilung Biomolekulare Mechanismen, Jahnstrasse 29, 69120 Heidelberg, Germany; and ^¶Maurice E. Müller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland

Edited by Carolyn Cohen, Brandeis University, Waltham, MA, and approved October 15, 2004 (received for review May 11, 2004)

Abstract

The vasodilator-stimulated phosphoprotein (VASP) is a key regulator of actin dynamics. We have determined the 1.3-Å resolution crystal structure of the 45-residue-long tetramerization domain (TD) from human VASP. This domain forms a right-handed α-helical coiled-coil structure with a similar degree of supercoiling as found in the widespread left-handed coiled coils with heptad repeats. The basis for the right-handed geometry of VASP TD is a 15-residue repeat in its amino acid sequence, which reveals a characteristic pattern of hydrophobic residues. Hydrophobic interactions and a network of salt bridges render VASP TD highly thermostable with a melting point of 120°C.

Footnotes

↵ § To whom correspondence may be addressed. E-mail: u.walter{at}medizin.uni-wuerzburg.de or alfred.wittinghofer{at}mpi-dortmund.mpg.de.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: TD, tetramerization domain; VASP, vasodilator-stimulated phosphoprotein; DSC, differential scanning calorimetry; EVH1/2, Ena-VASP homology 1/2.
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 1USE and 1USD for wild type and Leu253Met mutant, respectively).