PDBsum entry 2m55

Calcium binding protein/protein fibril

PDB id: 2m55

Contents

Protein chains

148 a.a.

21 a.a.

Metals

_CA ×4

PDB id:

2m55

Name:

Calcium binding protein/protein fibril

Title:

Nmr structure of the complex of an n-terminally acetylated alpha- synuclein peptide with calmodulin

Structure:

Calmodulin. Chain: a. Synonym: cam. Engineered: yes. Alpha-synuclein. Chain: b. Fragment: unp residues 1-19. Synonym: non-a beta component of ad amyloid, non-a4 component of amyloid precursor, nacp.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: calm1, calm, cam, cam1, calm2, cam2, camb, calm3, calml2, cam3, camc, camiii. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

NMR struc:

20 models

Authors:

J.M.Gruschus,T.Yap,S.Pistolesi,A.S.Maltsev,J.C.Lee

Key ref:

J.M.Gruschus et al. (2013). NMR structure of calmodulin complexed to an N-terminally acetylated α-synuclein peptide. Biochemistry, 52, 3436-3445. PubMed id: 23607618 DOI: 10.1021/bi400199p

Date:

13-Feb-13 Release date: 08-May-13

Protein chain

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 148 a.a.

Protein chain

P37840  (SYUA_HUMAN) -  Alpha-synuclein from Homo sapiens

Seq: 140 a.a.

Struc: 20 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1021/bi400199p

Biochemistry 52:3436-3445 (2013)

PubMed id: 23607618

NMR structure of calmodulin complexed to an N-terminally acetylated α-synuclein peptide.

J.M.Gruschus, T.L.Yap, S.Pistolesi, A.S.Maltsev, J.C.Lee.

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.