PDBsum entry 1iwq

Metal binding protein/protein binding

PDB id: 1iwq

Contents

Protein chains

139 a.a. *

18 a.a. *

Metals

_CA ×4

Waters ×86

* Residue conservation analysis

PDB id:

1iwq

Name:

Metal binding protein/protein binding

Title:

Crystal structure of marcks calmodulin binding domain peptide complexed with ca2+/calmodulin

Structure:

Calmodulin. Chain: a. Engineered: yes. Marcks. Chain: b. Fragment: calmodulin binding domain. Synonym: myristoylated alanine-rich c-kinase substrate. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this sequence occurs naturally in humans, mouse, rat and bovine.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.00Å R-factor: 0.225 R-free: 0.267

Authors:

E.Yamauchi,T.Nakatsu,M.Matsubara,H.Kato,H.Taniguchi,Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

E.Yamauchi et al. (2003). Crystal structure of a MARCKS peptide containing the calmodulin-binding domain in complex with Ca2+-calmodulin. Nat Struct Biol, 10, 226-231. PubMed id: 12577052 DOI: 10.1038/nsb900

Date:

31-May-02 Release date: 11-Mar-03

Protein chain

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 139 a.a.

Protein chain

P29966  (MARCS_HUMAN) -  Myristoylated alanine-rich C-kinase substrate from Homo sapiens

Seq: 332 a.a.

Struc: 18 a.a.

DOI no: 10.1038/nsb900

Nat Struct Biol 10:226-231 (2003)

PubMed id: 12577052

Crystal structure of a MARCKS peptide containing the calmodulin-binding domain in complex with Ca2+-calmodulin.

E.Yamauchi, T.Nakatsu, M.Matsubara, H.Kato, H.Taniguchi.

ABSTRACT

The calmodulin-binding domain of myristoylated alanine-rich C kinase substrate (MARCKS), which interacts with various targets including calmodulin, actin and membrane lipids, has been suggested to function as a crosstalk point among several signal transduction pathways. We present here the crystal structure at 2 A resolution of a peptide consisting of the MARCKS calmodulin (CaM)-binding domain in complex with Ca2+-CaM. The domain assumes a flexible conformation, and the hydrophobic pocket of the calmodulin N-lobe, which is a common CaM-binding site observed in previously resolved Ca2+-CaM-target peptide complexes, is not involved in the interaction. The present structure presents a novel target-recognition mode of calmodulin and provides insight into the structural basis of the flexible interaction module of MARCKS.

Selected figure(s)

Figure 1.
Figure 1. CaM-binding domain of MARCKS-related proteins. a, Schematic diagram of mouse MARCKS domain structure. The conventional full sequence of CaM-binding domain including basic cluster regions is shown. Sequences of 19-residue peptide are conserved among human, mouse, rat and bovine. Residues whose electron densities were observed in the present structure are underlined. Residues interacting with CaM are colored green for hydrophobic residues, red for basic residues and blue for serine residues. Key hydrophobic residues that interact either solely with N- or C-lobe of CaM -- Phe157 and Leu159 -- are boxed. The known phosphorylation sites are labeled with 'P'. b, Alignment of sequences of CaM-binding region of proteins with similar sequence characteristics. Key hydrophobic residues that may interact with hydrophobic pockets or surfaces are boxed. Conserved basic and hydrophobic residues are shown in red and green, respectively. Sequences shown are MLP (residues 87 -100)2, DAKAP200 (residues 128 -141)39, ADD1 (residues 717 -737)26, AKAP79 (residues 31 -52)28, RALA (residues 183 -200)27 and GRK (residues 20 -39)29.

Figure 2.
Figure 2. Comparison of the complex with other CaM -target peptide complexes. a, Ribbon representation of the MARCKS peptide -CaM complex compared with other globular-type CaM -target peptide complexes: MLCK (PDB entry 1CDL), CaMKII (1CDM) and CaMKK (1IQ5). The N- and C-lobe of CaM are shown in green and blue, respectively. The target peptides are shown in red. Ca^2+ ions are shown as black spheres. The figures were produced using MolScript40 and Raster3D^41. The target peptides are shown in red. The key hydrophobic residues of target peptides anchored to either of the N- or C-lobes of CaM are shown in ball-and-stick representations and labeled. Electrostatic surface representations of CaM N-lobe with b, MARCKS peptide and c, MLCK peptide^8 and C-lobe with d, edema factor (EF)19. In (d), only part of helix H of EF (residues 521 -537), which interacts with Ca^2+-bound C-lobe of CaM, was shown. The hydrophobic pocket of CaM observed in (c,d) is flattened in (b) and is not involved in the interaction with MARCKS peptide. Hydrophobic residues of MARCKS peptide interacting with CaM N-lobe, Leu159 and Phe162, are located on different hydrophobic surfaces of CaM. The figures were generated using GRASP42. e, Superimposition of CaM N-lobe of the MARCKS peptide -Ca^2+-CaM (yellow) onto those of the MLCK peptide -Ca^2+-CaM8 (green). The MARCKS and MLCK peptides are shown in red and orange, respectively.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2003, 10, 226-231) copyright 2003.

Figures were selected by an automated process.