uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The structural basis of actin interaction with multiple WH2/β thymosin motif-containing proteins
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Show others and affiliations
2006 In: Structure, Vol. 14, 469-76 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2006. Vol. 14, 469-76 p.
Identifiers
URN: urn:nbn:se:uu:diva-94970OAI: oai:DiVA.org:uu-94970DiVA: diva2:169008
Available from: 2006-10-18 Created: 2006-10-18Bibliographically approved
In thesis
1. Structural Study of the WH2 Family and Filamin: Implications for Actin Cytoskeleton Regulation
Open this publication in new window or tab >>Structural Study of the WH2 Family and Filamin: Implications for Actin Cytoskeleton Regulation
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cellular processes like motility, chemotaxis, phagocytosis and morphogenesis are dependent on the dynamic regulation of the actin cytoskeleton. This cytoskeleton system is tightly controlled by a number of diverse actin-binding proteins (ABPs) by various mechanisms described as nucleation, polymerization, capping, severing, depolymerization and sequestration. The ABPs are grouped based on sequence identity as in the Wiskott-Aldrich Syndrome protein homology domain 2 (WH2), and the calponin homology domain (CH) containing proteins.

In this work, we elucidate the crystal structures of hybrids of gelsolin domain 1 with thymosin β4, ciboulot domain 2, and the second WH2 domain of N-WASP each bound to actin. We show that the single WH2 motif containing protein thymosin β4 in part sequesters actin by binding its pointed end via a C-terminal helix. This interaction prevents the addition of bound actin protomers to the barbed end of the filament. We propose that sequence variations in some WH2 motifs conferred F-actin binding ability to multiple repeat-containing proteins. These F-actin binding domains interact with the barbed end of a filament and the adjacent WH2 motifs are then freed to add their bound actin to the growing filament end. We demonstrate the binding of ciboulot domains 2 and 3 to both G- and F-actin and that full length ciboulot is capable of binding two actin monomers simultaneously.

We have also cloned, expressed, purified and crystallized rod domains 14-16 from the actin crosslinking protein a-filamin. Preliminary X-ray crystallography data gives us hope that we shall be able to solve the structure of this triple domain repeat.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 182
Keyword
Biochemistry, Actin, Thymosin, Ciboulot, N-WASP, Filamin, Calponin homology domain, WH2, Protein Crystallography, Biokemi
Identifiers
urn:nbn:se:uu:diva-7188 (URN)91-554-6679-6 (ISBN)
Public defence
2006-11-08, C10:301, BMC, Hursagata 3, SE 751 23, Uppsala, 13:15
Opponent
Supervisors
Available from: 2006-10-18 Created: 2006-10-18Bibliographically approved

Open Access in DiVA

No full text

By organisation
Department of Medical Biochemistry and Microbiology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 445 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf