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PDBsum entry 2m55
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Calcium binding protein/protein fibril
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PDB id
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2m55
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References listed in PDB file
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Key reference
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Title
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Nmr structure of calmodulin complexed to an n-Terminally acetylated α-Synuclein peptide.
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Authors
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J.M.Gruschus,
T.L.Yap,
S.Pistolesi,
A.S.Maltsev,
J.C.Lee.
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Ref.
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Biochemistry, 2013,
52,
3436-3445.
[DOI no: ]
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PubMed id
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Abstract
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Calmodulin (CaM) is a calcium binding protein that plays numerous roles in
Ca-dependent cellular processes, including uptake and release of
neurotransmitters in neurons. α-Synuclein (α-syn), one of the most abundant
proteins in central nervous system neurons, helps maintain presynaptic vesicles
containing neurotransmitters and moderates their Ca-dependent release into the
synapse. Ca-Bound CaM interacts with α-syn most strongly at its N-terminus. The
N-terminal region of α-syn is important for membrane binding; thus, CaM could
modulate membrane association of α-syn in a Ca-dependent manner. In contrast,
Ca-free CaM has negligible interaction. The interaction with CaM leads to
significant signal broadening in both CaM and α-syn NMR spectra, most likely
due to conformational exchange. The broadening is much reduced when binding a
peptide consisting of the first 19 residues of α-syn. In neurons, most α-syn
is acetylated at the N-terminus, and acetylation leads to a 10-fold increase in
binding strength for the α-syn peptide (KD = 35 ± 10 μM). The N-terminally
acetylated peptide adopts a helical structure at the N-terminus with the acetyl
group contacting the N-terminal domain of CaM and with less ordered helical
structure toward the C-terminus of the peptide contacting the CaM C-terminal
domain. Comparison with known structures shows that the CaM/α-syn complex most
closely resembles Ca-bound CaM in a complex with an IQ motif peptide. However, a
search comparing the α-syn peptide sequence with known CaM targets, including
IQ motifs, found no homologies; thus, the N-terminal α-syn CaM binding site
appears to be a novel CaM target sequence.
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