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Metal binding protein PDB-id
1dyk
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Protein chain
374 a.a. *
Metal ions
_CA ×2
Waters ×251

* Residue conservation analysis
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PDB id: 1dyk
Name: Metal binding protein
Title: Laminin alpha 2 chain lg4-5 domain pair

Structure:
Laminin alpha 2 chain. Chain: a. Fragment: laminin g-like domain 4-5 pair. Engineered: yes. Mutation: yes

Source:
Mus musculus. House mouse. Organism_taxid: 10090. Strain: fvb/n. Tissue: embryo. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: ebna-293. Expression_system_cell: emryonic kidney cell.

UniProt:
Q60675 (LAMA2_MOUSE) Pfam   ArchSchema ?
Seq:
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Struc:
Seq: 3106 a.a.
Struc: 374 a.a.*
Key:    PfamA domain
 Secondary structure  CATH domain
* PDB and UniProt seqs differ at 24 residue positions (black crosses)

Resolution:
2.0Å

R-factor:
0.233

R-free:
0.261

Authors:
D.Tisi,J.F.Talts,R.Timple,E.Hohenester

Key ref:
D.Tisi et al. (2000). Structure of the C-terminal laminin G-like domain pair of the laminin alpha2 chain harbouring binding sites for alpha-dystroglycan and heparin.. EMBO J, 19, 1432-1440. [PubMed id: 10747011] [DOI: 10.1093/emboj/19.7.1432]

Date:
01-Feb-00

Release date:
04-Feb-01

Related entries:
1qu0 crystal structure of the fifth laminin g-like module of th mouse laminin alpha2 chain
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    Key reference    
 
 
DOI no: 10.1093/emboj/19.7.1432 EMBO J 19:1432-1440 (2000)
PubMed id: 10747011  
 
 
Structure of the C-terminal laminin G-like domain pair of the laminin alpha2 chain harbouring binding sites for alpha-dystroglycan and heparin.
D.Tisi, J.F.Talts, R.Timpl, E.Hohenester.
 
  ABSTRACT  
 
The laminins are large heterotrimeric glycoproteins with fundamental roles in basement membrane architecture and function. The C-terminus of the laminin alpha chain contains a tandem of five laminin G-like (LG) domains. We report the 2.0 A crystal structure of the laminin alpha2 LG4-LG5 domain pair, which harbours binding sites for heparin and the cell surface receptor alpha-dystroglycan, and is 41% identical to the laminin alpha1 E3 fragment. LG4 and LG5 are arranged in a V-shaped fashion related by a 110 degrees rotation about an axis passing near the domain termini. An extended N-terminal segment is disulfide bonded to LG5 and stabilizes the domain pair. Two calcium ions, one each in LG4 and LG5, are located 65 A apart at the tips of the domains opposite the polypeptide termini. An extensive basic surface region between the calcium sites is proposed to bind alpha-dystroglycan and heparin. The LG4-LG5 structure was used to construct a model of the laminin LG1-LG5 tandem and interpret missense mutations underlying protein S deficiency.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 (A) The LG4–LG5 interface. The colour scheme is the same as in Figure 1. Residues involved in inter-domain contacts are shown as ball-and-stick models and are labelled. The most prominent contact is centred on Phe2931 (see the text). (B) Interactions between the N-terminal segment (in brown) and LG5 (in green). Dashed lines indicate hydrogen bonds. The electron density shown is a simulated annealing 2F[obs] - F[calc] omit map at 2.0 Šresolution (1.5 contouring), in which the N-terminal segment and Cys3017 in LG5 were excluded from the phasing model.
Figure 4.
Figure 4 Calcium-binding sites in 2LG4–5. (A) Calcium 1 in LG4. The calcium ligands are shown as ball-and-stick models and are labelled. Calcium–ligand bonds are shown as black sticks. A metal-bound water molecule is shown in yellow. (B) Calcium 2 in LG5. The calcium coordination is similar to calcium 1, but Asp2861 from a packing-related molecule in the crystal (in yellow) occupies the fifth coordination site (see the text).
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2000, 19, 1432-1440) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19739104 J.Munoz, Y.Zhou, and H.W.Jarrett (2010).
LG4-5 domains of laminin-211 binds alpha-dystroglycan to allow myotube attachment and prevent anoikis.
  J Cell Physiol, 222, 111-119.  
18758940 B.Sauerzapfe, K.Krenek, J.Schmiedel, W.W.Wakarchuk, H.Pelantová, V.Kren, and L.Elling (2009).
Chemo-enzymatic synthesis of poly-N-acetyllactosamine (poly-LacNAc) structures and their characterization for CGL2-galectin-mediated binding of ECM glycoproteins to biomaterial surfaces.
  Glycoconj J, 26, 141-159.  
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
19180521 K.Umezawa, J.Ikebe, M.Nomizu, H.Nakamura, and J.Higo (2009).
Conformational requirement on peptides to exert laminin's activities and search for protein segments with laminin's activities.
  Biopolymers, 92, 124-131.  
19543532 N.P.Vogtländer, H.J.Visch, M.A.Bakker, J.H.Berden, and J.van der Vlag (2009).
Ligation of alpha-dystroglycan on podocytes induces intracellular signaling: a new mechanism for podocyte effacement?
  PLoS One, 4, e5979.  
18024432 B.P.Woodall, A.Nyström, R.A.Iozzo, J.A.Eble, S.Niland, T.Krieg, B.Eckes, A.Pozzi, and R.V.Iozzo (2008).
Integrin {alpha}2 1 Is the Required Receptor for Endorepellin Angiostatic Activity.
  J Biol Chem, 283, 2335-2343.  
18276595 M.M.Barroso, E.Freire, G.S.Limaverde, G.M.Rocha, E.J.Batista, G.Weissmüller, L.R.Andrade, and T.Coelho-Sampaio (2008).
Artificial laminin polymers assembled in acidic pH mimic basement membrane organization.
  J Biol Chem, 283, 11714-11720.  
17676646 C.Anderson, S.J.Winder, and A.G.Borycki (2007).
Dystroglycan protein distribution coincides with basement membranes and muscle differentiation during mouse embryogenesis.
  Dev Dyn, 236, 2627-2635.  
17449623 C.Geslin, M.Gaillard, D.Flament, K.Rouault, M.Le Romancer, D.Prieur, and G.Erauso (2007).
Analysis of the first genome of a hyperthermophilic marine virus-like particle, PAV1, isolated from Pyrococcus abyssi.
  J Bacteriol, 189, 4510-4519.  
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
17553797 V.M.Leppänen, H.Tossavainen, P.Permi, L.Lehtiö, G.Rönnholm, A.Goldman, I.Kilpelaïnen, and T.Pihlajamaa (2007).
Crystal structure of the N-terminal NC4 domain of collagen IX, a zinc binding member of the laminin-neurexin-sex hormone binding globulin (LNS) domain family.
  J Biol Chem, 282, 23219-23230.
PDB code: 2uur
16945929 K.Hozumi, N.Suzuki, P.K.Nielsen, M.Nomizu, and Y.Yamada (2006).
Laminin alpha1 chain LG4 module promotes cell attachment through syndecans and cell spreading through integrin alpha2beta1.
  J Biol Chem, 281, 32929-32940.  
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
16362042 T.Sasaki, P.G.Knyazev, N.J.Clout, Y.Cheburkin, W.Göhring, A.Ullrich, R.Timpl, and E.Hohenester (2006).
Structural basis for Gas6-Axl signalling.
  EMBO J, 25, 80-87.
PDB code: 2c5d
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.  
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.  
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.  
16219760 S.P.Smirnov, P.Barzaghi, K.K.McKee, M.A.Ruegg, and P.D.Yurchenco (2005).
Conjugation of LG domains of agrins and perlecan to polymerizing laminin-2 promotes acetylcholine receptor clustering.
  J Biol Chem, 280, 41449-41457.  
15326183 D.Bozic, F.Sciandra, D.Lamba, and A.Brancaccio (2004).
The structure of the N-terminal region of murine skeletal muscle alpha-dystroglycan discloses a modular architecture.
  J Biol Chem, 279, 44812-44816.
PDB code: 1u2c
14612440 K.Künneken, G.Pohlentz, A.Schmidt-Hederich, U.Odenthal, N.Smyth, J.Peter-Katalinic, P.Bruckner, and J.A.Eble (2004).
Recombinant human laminin-5 domains. Effects of heterotrimerization, proteolytic processing, and N-glycosylation on alpha3beta1 integrin binding.
  J Biol Chem, 279, 5184-5193.  
15037599 T.Sasaki, R.Fässler, and E.Hohenester (2004).
Laminin: the crux of basement membrane assembly.
  J Cell Biol, 164, 959-963.  
12826666 A.Utani, Y.Momota, H.Endo, Y.Kasuya, K.Beck, N.Suzuki, M.Nomizu, and H.Shinkai (2003).
Laminin alpha 3 LG4 module induces matrix metalloproteinase-1 through mitogen-activated protein kinase signaling.
  J Biol Chem, 278, 34483-34490.  
12542704 B.Saposnik, D.Borgel, M.Aiach, and S.Gandrille (2003).
Functional properties of the sex-hormone-binding globulin (SHBG)-like domain of the anticoagulant protein S.
  Eur J Biochem, 270, 545-555.  
12621054 C.N.Tseng, L.Zhang, M.Cascio, and Z.Z.Wang (2003).
Calcium plays a critical role in determining the acetylcholine receptor-clustering activities of alternatively spliced isoforms of Agrin.
  J Biol Chem, 278, 17236-17245.  
12556455 D.E.Michele, and K.P.Campbell (2003).
Dystrophin-glycoprotein complex: post-translational processing and dystroglycan function.
  J Biol Chem, 278, 15457-15460.  
14622018 M.Bozzi, M.Bianchi, F.Sciandra, M.Paci, B.Giardina, A.Brancaccio, and D.O.Cicero (2003).
Structural characterization by NMR of the natively unfolded extracellular domain of beta-dystroglycan: toward the identification of the binding epitope for alpha-dystroglycan.
  Biochemistry, 42, 13717-13724.  
12532327 Y.Kariya, Y.Tsubota, T.Hirosaki, H.Mizushima, W.Puzon-McLaughlin, Y.Takada, and K.Miyazaki (2003).
Differential regulation of cellular adhesion and migration by recombinant laminin-5 forms with partial deletion or mutation within the G3 domain of alpha3 chain.
  J Cell Biochem, 88, 506-520.  
12111737 H.J.Spence, Y.J.Chen, and S.J.Winder (2002).
Muscular dystrophies, the cytoskeleton and cell adhesion.
  Bioessays, 24, 542-552.  
12082085 S.Li, D.Harrison, S.Carbonetto, R.Fassler, N.Smyth, D.Edgar, and P.D.Yurchenco (2002).
Matrix assembly, regulation, and survival functions of laminin and its receptors in embryonic stem cell differentiation.
  J Cell Biol, 157, 1279-1290.  
11891340 S.M.Prince, M.Achtman, and J.P.Derrick (2002).
Crystal structure of the OpcA integral membrane adhesin from Neisseria meningitidis.
  Proc Natl Acad Sci U S A, 99, 3417-3421.
PDB code: 1k24
11886875 S.P.Smirnov, E.L.McDearmon, S.Li, J.M.Ervasti, K.Tryggvason, and P.D.Yurchenco (2002).
Contributions of the LG modules and furin processing to laminin-2 functions.
  J Biol Chem, 277, 18928-18937.  
12379663 T.Hirosaki, Y.Tsubota, Y.Kariya, K.Moriyama, H.Mizushima, and K.Miyazaki (2002).
Laminin-6 is activated by proteolytic processing and regulates cellular adhesion and migration differently from laminin-5.
  J Biol Chem, 277, 49287-49295.  
11856301 T.Sasaki, K.Mann, J.H.Miner, N.Miosge, and R.Timpl (2002).
Domain IV of mouse laminin beta1 and beta2 chains.
  Eur J Biochem, 269, 431-442.  
12218057 T.Sasaki, P.G.Knyazev, Y.Cheburkin, W.Göhring, D.Tisi, A.Ullrich, R.Timpl, and E.Hohenester (2002).
Crystal structure of a C-terminal fragment of growth arrest-specific protein Gas6. Receptor tyrosine kinase activation by laminin G-like domains.
  J Biol Chem, 277, 44164-44170.
PDB code: 1h30
12100448 T.Wibawa, H.Soebono, and M.Matsuo (2002).
Association of a missense mutation of the laminin alpha2 gene with tuberculoid type of leprosy in Indonesian patients.
  Trop Med Int Health, 7, 631-636.  
11276089 B.O.Villoutreix, B.Dahlbäck, D.Borgel, S.Gandrille, and Y.A.Muller (2001).
Three-dimensional model of the SHBG-like region of anticoagulant protein S: new structure-function insights.
  Proteins, 43, 203-216.  
11798066 M.Durbeej, J.F.Talts, M.D.Henry, P.D.Yurchenco, K.P.Campbell, and P.Ekblom (2001).
Dystroglycan binding to laminin alpha1LG4 module influences epithelial morphogenesis of salivary gland and lung in vitro.
  Differentiation, 69, 121-134.  
11470830 S.Sugita, F.Saito, J.Tang, J.Satz, K.Campbell, and T.C.Südhof (2001).
A stoichiometric complex of neurexins and dystroglycan in brain.
  J Cell Biol, 154, 435-445.  
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.