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Structure and calci...
Structure and calcium-binding studies of calmodulin-like domain of human non-muscle alpha-actinin-1
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Prebil, Sara Drmota (author)
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Slapsak, Urska (author)
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Pavsic, Miha (author)
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Ilc, Gregor (author)
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Puz, Vid (author)
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Ribeiro, Euripedes de Almeida (author)
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Anrather, Dorothea (author)
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Hartl, Markus (author)
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- Backman, Lars (author)
- Umeå universitet,Kemiska institutionen
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Plavec, Janez (author)
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Lenarcic, Brigita (author)
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Djinovic-Carugo, Kristina (author)
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(creator_code:org_t)
- 2016-06-07
- 2016
- English.
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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https://umu.diva-por... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- The activity of several cytosolic proteins critically depends on the concentration of calcium ions. One important intracellular calcium-sensing protein is alpha-actinin-1, the major actin crosslinking protein in focal adhesions and stress fibers. The actin crosslinking activity of alpha-actinin-1 has been proposed to be negatively regulated by calcium, but the underlying molecular mechanisms are poorly understood. To address this, we determined the first high-resolution NMR structure of its functional calmodulin-like domain (CaMD) in calcium-bound and calcium-free form. These structures reveal that in the absence of calcium, CaMD displays a conformationally flexible ensemble that undergoes a structural change upon calcium binding, leading to limited rotation of the N- and C-terminal lobes around the connecting linker and consequent stabilization of the calcium-loaded structure. Mutagenesis experiments, coupled with mass-spectrometry and isothermal calorimetry data designed to validate the calcium binding stoichiometry and binding site, showed that human non-muscle alpha-actinin-1 binds a single calcium ion within the N-terminal lobe. Finally, based on our structural data and analogy with other alpha-actinins, we provide a structural model of regulation of the actin crosslinking activity of alpha-actinin-1 where calcium induced structural stabilisation causes fastening of the juxtaposed actin binding domain, leading to impaired capacity to crosslink actin.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Prebil, Sara Drm ...
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Slapsak, Urska
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Pavsic, Miha
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Ilc, Gregor
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Puz, Vid
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Ribeiro, Euriped ...
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show more...
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Anrather, Doroth ...
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Hartl, Markus
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Backman, Lars
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Plavec, Janez
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Lenarcic, Brigit ...
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Djinovic-Carugo, ...
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Scientific Repor ...
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Umeå University