PDBsum entry 1okq

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protein metals links
Metal binding protein PDB id
Protein chain
374 a.a. *
Waters ×38
* Residue conservation analysis
PDB id:
Name: Metal binding protein
Title: Laminin alpha 2 chain lg4-5 domain pair, ca1 site mutant
Structure: Laminin alpha 2 chain. Chain: a. Fragment: laminin g-like domain 4-5 pair, residues 2729-3093. Engineered: yes. Mutation: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Strain: fvb/n. Cell_line: ebna-293. Tissue: embryo. Cell: emryonic kidney cell. Expressed in: homo sapiens. Expression_system_taxid: 9606.
2.0Å     R-factor:   0.220     R-free:   0.270
Authors: H.Wizemann,J.H.O.Garbe,M.V.K.Friedrich,R.Timpl,T.Sasaki, E.Hohenester
Key ref:
H.Wizemann et al. (2003). Distinct requirements for heparin and alpha-dystroglycan binding revealed by structure-based mutagenesis of the laminin alpha2 LG4-LG5 domain pair. J Mol Biol, 332, 635-642. PubMed id: 12963372 DOI: 10.1016/S0022-2836(03)00848-9
28-Jul-03     Release date:   11-Sep-03    
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Protein chain
Pfam   ArchSchema ?
Q60675  (LAMA2_MOUSE) -  Laminin subunit alpha-2
3118 a.a.
374 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)


DOI no: 10.1016/S0022-2836(03)00848-9 J Mol Biol 332:635-642 (2003)
PubMed id: 12963372  
Distinct requirements for heparin and alpha-dystroglycan binding revealed by structure-based mutagenesis of the laminin alpha2 LG4-LG5 domain pair.
H.Wizemann, J.H.Garbe, M.V.Friedrich, R.Timpl, T.Sasaki, E.Hohenester.
Laminin-2 (alpha2beta1gamma1) is found in basement membranes surrounding muscle and peripheral nerve cells. Several types of cellular receptors bind to the laminin G-like (LG) domains at the C terminus of the alpha2 chain, the interaction with alpha-dystroglycan (alpha-DG) being particularly important in muscle. We have used site-directed mutagenesis and in vitro binding assays to map the binding sites on the laminin alpha2 chain LG4-LG5 domain pair for alpha-DG, heparin and sulfatides. Calcium-dependent alpha-DG recognition requires the calcium ion in LG4, but not the one in LG5, as well as basic residues in both LG domains. Heparin and sulfatides also bind to basic residues in both LG domains, but there is little overlap in the binding sites for alpha-DG and heparin/sulfatides. The results should prove useful for the molecular dissection of laminin-receptor interactions in vivo.
  Selected figure(s)  
Figure 1.
Figure 1. (a) Electrostatic surface representation of the laminin a2 LG4-LG5 structure.[14.] Positive and negative potential are represented by blue and red colouring, respectively. The Figure was made with GRASP. [31.] (b) Ca trace of the laminin a2 LG4-LG5 structure in the same orientation, with amino acid side-chains mutated in the present study shown as ball-and-stick models. Basic and acidic residues are coloured blue and red, respectively, and calcium ions are shown as pink spheres. The Figure was made with BOBSCRIPT [32.] and RASTER3D. [33.]
Figure 4.
Figure 4. Stereoview of the mutated calcium binding site in the laminin a2 LG4-LG5 D2808A/D2876A mutant. The wild-type structure is superimposed for comparison and shown in light blue. The F[obs] -F[calc] difference electron density map is shown in green at the +3s level.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 332, 635-642) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20657839 K.I.Gawlik, M.Akerlund, V.Carmignac, H.Elamaa, and M.Durbeej (2010).
Distinct roles for laminin globular domains in laminin alpha1 chain mediated rescue of murine laminin alpha2 chain deficiency.
  PLoS One, 5, e11549.  
19800000 N.Suzuki, K.Hozumi, S.Urushibata, T.Yoshimura, Y.Kikkawa, J.D.Gumerson, D.E.Michele, M.P.Hoffman, Y.Yamada, and M.Nomizu (2010).
Identification of alpha-dystroglycan binding sequences in the laminin alpha2 chain LG4-5 module.
  Matrix Biol, 29, 143-151.  
19553699 F.Carafoli, N.J.Clout, and E.Hohenester (2009).
Crystal structure of the LG1-3 region of the laminin alpha2 chain.
  J Biol Chem, 284, 22786-22792.
PDB code: 2wjs
19451276 J.Câmara, Z.Wang, C.Nunes-Fonseca, H.C.Friedman, M.Grove, D.L.Sherman, N.H.Komiyama, S.G.Grant, P.J.Brophy, A.Peterson, and C.ffrench-Constant (2009).
Integrin-mediated axoglial interactions initiate myelination in the central nervous system.
  J Cell Biol, 185, 699-712.  
19124151 K.Hozumi, N.Yamagata, D.Otagiri, C.Fujimori, Y.Kikkawa, Y.Kadoya, and M.Nomizu (2009).
Mixed peptide-chitosan membranes to mimic the biological activities of a multifunctional laminin alpha1 chain LG4 module.
  Biomaterials, 30, 1596-1603.  
19355968 P.D.Yurchenco, and B.L.Patton (2009).
Developmental and pathogenic mechanisms of basement membrane assembly.
  Curr Pharm Des, 15, 1277-1294.  
19762914 S.Y.Jung, J.M.Kim, H.K.Kang, d.a. .H.Jang, and B.M.Min (2009).
A biologically active sequence of the laminin alpha2 large globular 1 domain promotes cell adhesion through syndecan-1 by inducing phosphorylation and membrane localization of protein kinase Cdelta.
  J Biol Chem, 284, 31764-31775.  
18219670 J.H.Miner (2008).
Laminins and their roles in mammals.
  Microsc Res Tech, 71, 349-356.  
18982058 O.Thompson, I.Kleino, L.Crimaldi, M.Gimona, K.Saksela, and S.J.Winder (2008).
Dystroglycan, Tks5 and Src mediated assembly of podosomes in myoblasts.
  PLoS ONE, 3, e3638.  
17649979 C.O.Sallum, R.A.Kammerer, and A.T.Alexandrescu (2007).
Thermodynamic and structural studies of carbohydrate binding by the agrin-G3 domain.
  Biochemistry, 46, 9541-9550.  
17307732 D.Harrison, S.A.Hussain, A.C.Combs, J.M.Ervasti, P.D.Yurchenco, and E.Hohenester (2007).
Crystal structure and cell surface anchorage sites of laminin alpha1LG4-5.
  J Biol Chem, 282, 11573-11581.
PDB code: 2jd4
17949279 O.Siala, N.Louhichi, C.Triki, M.Morinière, A.Rebai, P.Richard, P.Guicheney, F.Baklouti, and F.Fakhfakh (2007).
Severe MDC1A congenital muscular dystrophy due to a splicing mutation in the LAMA2 gene resulting in exon skipping and significant decrease of mRNA level.
  Genet Test, 11, 199-207.  
17426950 S.Schéele, A.Nyström, M.Durbeej, J.F.Talts, M.Ekblom, and P.Ekblom (2007).
Laminin isoforms in development and disease.
  J Mol Med, 85, 825-836.  
17638854 T.J.Mankelow, N.Burton, F.O.Stefansdottir, F.A.Spring, S.F.Parsons, J.S.Pedersen, C.L.Oliveira, D.Lammie, T.Wess, N.Mohandas, J.A.Chasis, R.L.Brady, and D.J.Anstee (2007).
The Laminin 511/521-binding site on the Lutheran blood group glycoprotein is located at the flexible junction of Ig domains 2 and 3.
  Blood, 110, 3398-3406.
PDB codes: 2pet 2pf6
16772286 L.R.Sheckler, L.Henry, S.Sugita, T.C.Südhof, and G.Rudenko (2006).
Crystal structure of the second LNS/LG domain from neurexin 1alpha: Ca2+ binding and the effects of alternative splicing.
  J Biol Chem, 281, 22896-22905.
PDB code: 2h0b
15930001 A.Fallahi, B.Kroll, L.R.Warner, R.J.Oxford, K.M.Irwin, L.M.Mercer, S.E.Shadle, and J.T.Oxford (2005).
Structural model of the amino propeptide of collagen XI alpha1 chain with similarity to the LNS domains.
  Protein Sci, 14, 1526-1537.  
15920757 A.Sgambato, and A.Brancaccio (2005).
The dystroglycan complex: from biology to cancer.
  J Cell Physiol, 205, 163-169.  
15591058 E.M.Gonzalez, C.C.Reed, G.Bix, J.Fu, Y.Zhang, B.Gopalakrishnan, D.S.Greenspan, and R.V.Iozzo (2005).
BMP-1/Tolloid-like metalloproteases process endorepellin, the angiostatic C-terminal fragment of perlecan.
  J Biol Chem, 280, 7080-7087.  
16147852 N.Suzuki, F.Yokoyama, and M.Nomizu (2005).
Functional sites in the laminin alpha chains.
  Connect Tissue Res, 46, 142-152.  
16064139 R.V.Iozzo (2005).
Basement membrane proteoglycans: from cellar to ceiling.
  Nat Rev Mol Cell Biol, 6, 646-656.  
15824137 S.Li, P.Liquari, K.K.McKee, D.Harrison, R.Patel, S.Lee, and P.D.Yurchenco (2005).
Laminin-sulfatide binding initiates basement membrane assembly and enables receptor signaling in Schwann cells and fibroblasts.
  J Cell Biol, 169, 179-189.  
15016366 J.Stetefeld, A.T.Alexandrescu, M.W.Maciejewski, M.Jenny, K.Rathgeb-Szabo, T.Schulthess, R.Landwehr, S.Frank, M.A.Ruegg, and R.A.Kammerer (2004).
Modulation of agrin function by alternative splicing and Ca2+ binding.
  Structure, 12, 503-515.
PDB codes: 1pz7 1pz8 1pz9 1q56
15037599 T.Sasaki, R.Fässler, and E.Hohenester (2004).
Laminin: the crux of basement membrane assembly.
  J Cell Biol, 164, 959-963.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.