Sitar, Tomasz, Gallinger, Julia, Ducka, Anna M., Ikonen, Teemu P., Wohlhoefler, Michael, Schmoller, Kurt M., Bausch, Andreas R., Joel, Peteranne, Trybus, Kathleen M., Noegel, Angelika A., Schleicher, Michael, Huber, Robert and Holak, Tad A. (2011). Molecular architecture of the Spire-actin nucleus and its implication for actin filament assembly. Proc. Natl. Acad. Sci. U. S. A., 108 (49). S. 19575 - 19581. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

The Spire protein is a multifunctional regulator of actin assembly. We studied the structures and properties of Spire-actin complexes by X-ray scattering, X-ray crystallography, total internal reflection fluorescence microscopy, and actin polymerization assays. We show that Spire-actin complexes in solution assume a unique, longitudinal- like shape, in which Wiskott-Aldrich syndrome protein homology 2 domains (WH2), in an extended configuration, line up actins along the long axis of the core of the Spire-actin particle. In the complex, the kinase noncatalytic C-lobe domain is positioned at the side of the first N-terminal Spire-actin module. In addition, we find that preformed, isolated Spire-actin complexes are very efficient nucleators of polymerization and afterward dissociate from the growing filament. However, under certain conditions, all Spire constructs-even a single WH2 repeat-sequester actin and disrupt existing filaments. This molecular and structural mechanism of actin polymerization by Spire should apply to other actin-binding proteins that contain WH2 domains in tandem.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Sitar, TomaszUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gallinger, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ducka, Anna M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ikonen, Teemu P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wohlhoefler, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmoller, Kurt M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bausch, Andreas R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Joel, PeteranneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trybus, Kathleen M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noegel, Angelika A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schleicher, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huber, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holak, Tad A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-483601
DOI: 10.1073/pnas.1115465108
Journal or Publication Title: Proc. Natl. Acad. Sci. U. S. A.
Volume: 108
Number: 49
Page Range: S. 19575 - 19581
Date: 2011
Publisher: NATL ACAD SCIENCES
Place of Publication: WASHINGTON
ISSN: 0027-8424
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ALDRICH-SYNDROME PROTEIN; NUCLEATION FACTOR; ARP2/3 COMPLEX; STRUCTURAL BASIS; DOMAIN; FORMIN; POLYMERIZATION; SCATTERING; CAPPUCCINO; MECHANISMMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48360

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