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PDBsum entry 3f31
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Actin binding, structural protein
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PDB id
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3f31
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the nonerythroid alpha-Spectrin tetramerization site reveals differences between erythroid and nonerythroid spectrin tetramer formation.
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Authors
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S.Mehboob,
Y.Song,
M.Witek,
F.Long,
B.D.Santarsiero,
M.E.Johnson,
L.W.Fung.
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Ref.
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J Biol Chem, 2010,
285,
14572-14584.
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PubMed id
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Abstract
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We have solved the crystal structure of a segment of nonerythroid alpha-spectrin
(alphaII) consisting of the first 147 residues to a resolution of 2.3 A. We find
that the structure of this segment is generally similar to a corresponding
segment from erythroid alpha-spectrin (alphaI) but exhibits unique differences
with functional significance. Specific features include the following: (i) an
irregular and frayed first helix (Helix C'); (ii) a helical conformation in the
junction region connecting Helix C' with the first structural domain (D1); (iii)
a long A(1)B(1) loop in D1; and (iv) specific inter-helix hydrogen bonds/salt
bridges that stabilize D1. Our findings suggest that the hydrogen bond networks
contribute to structural domain stability, and thus rigidity, in alphaII, and
the lack of such hydrogen bond networks in alphaI leads to flexibility in
alphaI. We have previously shown the junction region connecting Helix C' to D1
to be unstructured in alphaI (Park, S., Caffrey, M. S., Johnson, M. E., and
Fung, L. W. (2003) J. Biol. Chem. 278, 21837-21844) and now find it to be
helical in alphaII, an important difference for alpha-spectrin association with
beta-spectrin in forming tetramers. Homology modeling and molecular dynamics
simulation studies of the structure of the tetramerization site, a triple
helical bundle of partial domain helices, show that mutations in alpha-spectrin
will affect Helix C' structural flexibility and/or the junction region
conformation and may alter the equilibrium between spectrin dimers and tetramers
in cells. Mutations leading to reduced levels of functional tetramers in cells
may potentially lead to abnormal neuronal functions.
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