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PDBsum entry 2n8z
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Calcium binding protein
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PDB id
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2n8z
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PDB id:
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| Name: |
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Calcium binding protein
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Title:
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Apo form of calmodulin-like domain of human non-muscle alpha-actinin 1
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Structure:
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Alpha-actinin-1. Chain: a. Fragment: ef-hand domains 1 and 2, residues 743-892. Synonym: alpha-actinin cytoskeletal isoform, f-actin cross-linking protein, non-muscle alpha-actinin-1. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: actn1. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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NMR struc:
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20 models
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Authors:
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S.Drmota Prebil,U.Slapsak,E.De Almeida Ribeiro,M.Pavsic,G.Ilc, K.Zielinska,M.Hartl,L.Backman,J.Plavec,B.Lenarcic,K.Djinovic-Carugo
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Key ref:
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S.Drmota Prebil
et al.
(2016).
Structure and calcium-binding studies of calmodulin-like domain of human non-muscle α-actinin-1.
Sci Rep,
6,
27383.
PubMed id:
DOI:
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Date:
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28-Oct-15
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Release date:
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29-Jun-16
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PROCHECK
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Headers
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References
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P12814
(ACTN1_HUMAN) -
Alpha-actinin-1 from Homo sapiens
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Seq:
Struc:
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892 a.a.
153 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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*
PDB and UniProt seqs differ
at 3 residue positions (black
crosses)
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DOI no:
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Sci Rep
6:27383
(2016)
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PubMed id:
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Structure and calcium-binding studies of calmodulin-like domain of human non-muscle α-actinin-1.
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S.Drmota Prebil,
U.Slapšak,
M.Pavšič,
G.Ilc,
V.Puž,
E.de Almeida Ribeiro,
D.Anrather,
M.Hartl,
L.Backman,
J.Plavec,
B.Lenarčič,
K.Djinović-Carugo.
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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 α-actinin-1, the major actin crosslinking protein in focal adhesions
and stress fibers. The actin crosslinking activity of α-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
α-actinin-1 binds a single calcium ion within the N-terminal lobe. Finally,
based on our structural data and analogy with other α-actinins, we provide a
structural model of regulation of the actin crosslinking activity of
α-actinin-1 where calcium induced structural stabilisation causes fastening of
the juxtaposed actin binding domain, leading to impaired capacity to crosslink
actin.
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Links
