2M55

NMR structure of the complex of an N-terminally acetylated alpha-synuclein peptide with calmodulin

Summary for 2M55

• Entry DOI: 10.2210/pdb2m55/pdb
• NMR Information: BMRB: 19036
• Descriptor: Calmodulin, Alpha-synuclein, CALCIUM ION (3 entities in total)
• Functional Keywords: protein/peptide, ca-binding, calcium binding protein-protein fibril complex, calcium binding protein/protein fibril
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, cytoskeleton, spindle: P62158; Cytoplasm: P37840
• Total number of polymer chains: 2
• Total formula weight: 18861.07

Authors

Gruschus, J.M.,Yap, T.,Pistolesi, S.,Maltsev, A.S.,Lee, J.C. (deposition date: 2013-02-13, release date: 2013-05-08, Last modification date: 2024-10-16)

Primary citation

Gruschus, J.M.,Yap, T.L.,Pistolesi, S.,Maltsev, A.S.,Lee, J.C.
NMR Structure of Calmodulin Complexed to an N-Terminally Acetylated alpha-Synuclein Peptide.
Biochemistry, 52:3436-3445, 2013

PubMed Abstract: 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.

PubMed: 23607618
DOI: 10.1021/bi400199p

Experimental method

SOLUTION NMR