PDBsum entry 1gg3

Membrane protein

PDB id: 1gg3

Contents

Protein chain

279 a.a. *

* Residue conservation analysis

PDB id:

1gg3

Name:

Membrane protein

Title:

Crystal structure of the protein 4.1r membrane binding domain

Structure:

Erythroid membrane protein 4.1r. Chain: a, b, c. Synonym: 4.1r. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.80Å R-factor: 0.226 R-free: 0.276

Authors:

B.G.Han

Key ref:

B.G.Han et al. (2000). Protein 4.1R core domain structure and insights into regulation of cytoskeletal organization. Nat Struct Biol, 7, 871-875. PubMed id: 11017195 DOI: 10.1038/82819

Date:

11-Jul-00 Release date: 10-Jan-01

Protein chains

P11171  (41_HUMAN) -  Protein 4.1 from Homo sapiens

Seq: 864 a.a.

Struc: 279 a.a.

DOI no: 10.1038/82819

Nat Struct Biol 7:871-875 (2000)

PubMed id: 11017195

Protein 4.1R core domain structure and insights into regulation of cytoskeletal organization.

B.G.Han, W.Nunomura, Y.Takakuwa, N.Mohandas, B.K.Jap.

ABSTRACT

The crystal structure of the core domain (N-terminal 30 kDa domain) of cytoskeletal protein 4.1R has been determined and shows a cloverleaf-like architecture. Each lobe of the cloverleaf contains a specific binding site for either band 3, glycophorin C/D or p55. At a central region of the molecule near where the three lobes are joined are two separate calmodulin (CaM) binding regions. One of these is composed primarily of an alpha-helix and is Ca 2+ insensitive; the other takes the form of an extended structure and its binding with CaM is dramatically enhanced by the presence of Ca 2+, resulting in the weakening of protein 4.1R binding to its target proteins. This novel architecture, in which the three lobes bind with three membrane associated proteins, and the location of calmodulin binding sites provide insight into how the protein 4.1R core domain interacts with membrane proteins and dynamically regulates cell shape in response to changes in intracellular Ca2+ levels.

Selected figure(s)

Figure 2.
Figure 2. Space filling representation and stereo view of the protein 4.1R core domain showing the binding regions for band 3, glycophorin C/D, p55 and CaM. The color code for the binding regions of band 3, glycophorin C/D, p55 and CaM is the same as that used in Fig. 1d. a, Space filling representation of the surface of the protein 4.1R core domain. Negatively charged residues from the GPC binding region and positively charged residues from the p55 binding region are colored in a darker hue. Key amino acid residues that have been shown to be critical for CaM binding are labeled: Ser 185 in the Ca^2+ sensitive CaM binding region; and Trp 268, Phe 277, and Phe 278 in the Ca^2+ insensitive CaM binding region. Tyr 41 from the band 3 binding sequence and Glu 246 from the p55 binding region are also labeled. b, Space filling representation viewed from the opposite side of the molecule shown in (a). Asp 216 and Glu 246 from the p55 binding region are labeled. c, Stereo view in the same orientation as that in (a). Binding regions for band 3, glycophorin C/D, and p55 are displayed in a translucent space filling representation while CaM binding regions are presented as ball-and-stick models. The Ca^ 2+ sensitive CaM binding sequence (red) is organized in an extended structure while the Ca^2+ insensitive CaM binding sequence (yellow) shows -helical structure.

Figure 3.
Figure 3. Space filling representations of CaM binding regions. Amino acid residues on the surface are labeled. Hydrophobic residues of the CaM binding sequence are colored white, polar residues yellow, negatively charged residues red, and positively charged residues blue. Key amino acid residues for CaM binding are labeled red. Hydrophobic residues from distant regions of the primary sequence that have folded to participate in the formation of the hydrophobic patch of the CaM binding region are shown in translucent white. a, Ca^2+ insensitive CaM binding region showing a hydrophobic patch flanked by predominantly positively charged residues. This patch has a high degree of complementarity to the target peptide binding surface of the CaM globular domain, which has a hydrophobic patch flanked by negatively charged residues. Such complementarity is believed to be a critical factor in CaM−target peptide interactions. Hydrophobic residues (Trp 268, Phe 277 and Phe 278) of protein 4.1R are known to be critical for CaM binding; replacement of these residues with Ala greatly affects CaM binding. The point mutation W268S results in CaM binding becoming Ca^2+ sensitive. b, Ca^2+ sensitive CaM binding region showing a hydrophobic patch and the distribution of charged residues. This region is formed by an extended structure. The polar residue Ser 185 is found to be important for Ca^2+ dependent interactions with CaM; the mutation S185W increases the binding affinity between this site and CaM and abolishes the Ca^2+ dependence.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 871-875) copyright 2000.

Figures were selected by an automated process.