PDBsum entry 2jd4

Metal binding protein

PDB id: 2jd4

Contents

Protein chains

376 a.a. *

Metals

_CL ×3

_MG ×4

Waters ×327

* Residue conservation analysis

PDB id:

2jd4

Name:

Metal binding protein

Title:

Mouse laminin alpha1 chain, domains lg4-5

Structure:

Laminin subunit alpha-1. Chain: a, b. Fragment: domains lg4-5, residues 2706-3084. Synonym: laminin alpha1 chain, laminin a chain. Engineered: yes. Mutation: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: 293-ebna.

Resolution:

1.90Å R-factor: 0.230 R-free: 0.262

Authors:

D.Harrison,S.A.Hussain,A.C.Combs,J.M.Ervasti,P.D.Yurchenco, E.Hohenester

Key ref:

D.Harrison et al. (2007). Crystal structure and cell surface anchorage sites of laminin alpha1LG4-5. J Biol Chem, 282, 11573-11581. PubMed id: 17307732 DOI: 10.1074/jbc.M610657200

Date:

04-Jan-07 Release date: 27-Feb-07

Protein chains

P19137  (LAMA1_MOUSE) -  Laminin subunit alpha-1 from Mus musculus

Seq: 3083 a.a.

Struc: 376 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1074/jbc.M610657200

J Biol Chem 282:11573-11581 (2007)

PubMed id: 17307732

Crystal structure and cell surface anchorage sites of laminin alpha1LG4-5.

D.Harrison, S.A.Hussain, A.C.Combs, J.M.Ervasti, P.D.Yurchenco, E.Hohenester.

ABSTRACT

The laminin G-like (LG) domains of laminin-111, a glycoprotein widely expressed during embryogenesis, provide cell anchoring and receptor binding sites that are involved in basement membrane assembly and cell signaling. We now report the crystal structure of the laminin alpha1LG4-5 domains and provide a mutational analysis of heparin, alpha-dystroglycan, and galactosylsulfatide binding. The two domains of alpha1LG4-5 are arranged in a V-shaped fashion similar to that observed with laminin alpha2 LG4-5 but with a substantially different interdomain angle. Recombinant alpha1LG4-5 binding to heparin, alpha-dystroglycan, and sulfatides was dependent upon both shared and unique contributions from basic residues distributed in several clusters on the surface of LG4. For heparin, the greatest contribution was detected from two clusters, 2719RKR and 2791KRK. Binding to alpha-dystroglycan was particularly dependent on basic residues within 2719RKR, 2831RAR, and 2858KDR. Binding to galactosylsulfatide was most affected by mutations in 2831RAR and 2766KGRTK but not in 2719RKR. The combined analysis of structure and activities reveal differences in LG domain interactions that should enable dissection of biological roles of different laminin ligands.

Selected figure(s)

Figure 1.
FIGURE 1. Structure of laminin 1LG4-5. A, superposition of the two 1LG4-5 molecules in the asymmetric unit. Molecules A (mol A; light brown) and B (mol B; blue) were superimposed on their LG4 domains. The position of Tyr^2871 (see"Results") is indicated. B, schematic diagram of molecule B (cyan, LG4; green, LG5). The N and C termini are labeled. Disulfide bonds are shown as yellow ball-and-stick models. Metal ions are shown as purple spheres. The positions of Asn^2714 and Asn^2811 (N-linked glycosylation sites) and Cys^3014 (unpaired cysteine) are indicated. The third glycosylation site at Asn^2900 is located at the back of LG5.

Figure 2.
FIGURE 2. Comparison of 1LG4-5 and 2LG4-5. A, sequence alignment of 1LG4-5 and 2LG4-5. Identical residues are shaded yellow, cysteines are shaded black, and metal ion ligands are shaded purple. The sequence numbering and -strands of mouse 1LG4-5 are indicated above the alignment, and the sequence numbering of mouse 2LG4-5 is indicated below the alignment. Residues implicated in receptor binding to 1LG4-5 (this work) and 2LG4-5 (13) are indicated in red. B, superposition of 1LG4 (this work) and 2LG4 (8). A total of 148 C atoms were superimposed with a root mean square deviation of 0.91 Å. C, superposition of 1LG5 (this work) and 2LG5 (8). A total of 153 C atoms were superimposed with a root mean square deviation of 0.59 Å.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 11573-11581) copyright 2007.

Figures were selected by an automated process.