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Structural Study of...
Structural Study of the WH2 Family and Filamin: Implications for Actin Cytoskeleton Regulation
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- Aguda, Adeleke H., 1969- (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Robinson, Robert (thesis advisor)
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Rask, Lars (thesis advisor)
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- Backman, Lars (opponent)
- Biochemistry, Umea
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(creator_code:org_t)
- ISBN 9155466796
- Uppsala : Acta Universitatis Upsaliensis, 2006
- English 54 s.
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Series: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 182
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Abstract
Subject headings
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- 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.
Keyword
- Biochemistry
- Actin
- Thymosin
- Ciboulot
- N-WASP
- Filamin
- Calponin homology domain
- WH2
- Protein Crystallography
- Biokemi
Publication and Content Type
- vet (subject category)
- dok (subject category)
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