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PDBsum entry 1szb

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protein metals Protein-protein interface(s) links
Protein binding PDB id
1szb
Jmol
Contents
Protein chain
167 a.a. *
Metals
_CA ×4
Waters ×144
* Residue conservation analysis
PDB id:
1szb
Name: Protein binding
Title: Crystal structure of the human mbl-associated protein 19 (map19)
Structure: Mannose binding lectin-associated serine protease-2 related protein, map19 (19kda). Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: masp2. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.261     R-free:   0.316
Authors: L.A.Gregory,N.M.Thielens,G.J.Arlaud,J.C.Fontecilla-Camps, C.Gaboriaud
Key ref:
L.A.Gregory et al. (2004). The X-ray structure of human mannan-binding lectin-associated protein 19 (MAp19) and its interaction site with mannan-binding lectin and L-ficolin. J Biol Chem, 279, 29391-29397. PubMed id: 15117939 DOI: 10.1074/jbc.M402687200
Date:
05-Apr-04     Release date:   22-Jun-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O00187  (MASP2_HUMAN) -  Mannan-binding lectin serine protease 2
Seq:
Struc:
 
Seq:
Struc:
686 a.a.
167 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.104  - Mannan-binding lectin-associated serine protease-2.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     calcium ion binding     1 term  

 

 
DOI no: 10.1074/jbc.M402687200 J Biol Chem 279:29391-29397 (2004)
PubMed id: 15117939  
 
 
The X-ray structure of human mannan-binding lectin-associated protein 19 (MAp19) and its interaction site with mannan-binding lectin and L-ficolin.
L.A.Gregory, N.M.Thielens, M.Matsushita, R.Sorensen, G.J.Arlaud, J.C.Fontecilla-Camps, C.Gaboriaud.
 
  ABSTRACT  
 
MAp19 is an alternative splicing product of the MASP-2 gene comprising the N-terminal CUB1-epidermal growth factor (EGF) segment of MASP-2, plus four additional residues at its C-terminal end. Like full-length MASP-2, it forms Ca(2+)-dependent complexes with mannan-binding lectin (MBL) and L-ficolin. The x-ray structure of human MAp19 was solved to a resolution of 2.5 A. It shows a head to tail homodimer held together by interactions between the CUB1 module of one monomer and the EGF module of its counterpart. A Ca(2+) ion bound to each EGF module stabilizes the dimer interfaces. A second Ca(2+) ion is bound to the distal end of each CUB1 module, through six ligands contributed by Glu(52), Asp(60), Asp(105), Ser(107), Asn(108), and a water molecule. Compared with its counterpart in human C1s, the N-terminal end of the MAp19 CUB1 module contains a 7-residue extension that forms additional inter-monomer contacts. To identify the residues involved in the interaction of MAp19 with MBL and L-ficolin, point mutants were generated and their binding ability was determined using surface plasmon resonance spectroscopy. Six mutations at Tyr(59), Asp(60), Glu(83), Asp(105), Tyr(106), and Glu(109) either strongly decreased or abolished interaction with both MBL and L-ficolin. These mutations map a common binding site for these proteins located at the distal end of each CUB1 module and stabilized by the Ca(2+) ion.
 
  Selected figure(s)  
 
Figure 4.
FIG. 4. Analysis by surface plasmon resonance spectroscopy of the interaction between the MAp19 variants and immobilized MBL or L-ficolin. A, interaction with MBL. B, interaction with L-ficolin. MBL and L-ficolin were immobilized on the sensor chip as described under "Experimental Procedures." Wild-type MAp19 and its Y59A, D60A, E83A, D105G, Y106A, and E109A mutants were each injected at a concentration of 50 nM.
Figure 6.
FIG. 6. The MBL/L-ficolin interaction site of human MAp19. A, top view of the MAp19 dimer structure. The closed and open circles indicate the two MBL-binding sites proposed by Feinberg et al. (21). B, proposed model of the interaction between MAp19 and MBL. The MAp19 mutations that inhibit interaction with MBL and L-ficolin are shown in red, and those that have no significant effect are shown in yellow. C, stereo view of Ca^2+-binding site II and the proposed interaction site in MAp19.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 29391-29397) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21315829 Y.Endo, M.Matsushita, and T.Fujita (2011).
The role of ficolins in the lectin pathway of innate immunity.
  Int J Biochem Cell Biol, 43, 705-712.  
20237569 C.B.Andersen, M.Madsen, T.Storm, S.K.Moestrup, and G.R.Andersen (2010).
Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes.
  Nature, 464, 445-448.
PDB code: 3kq4
19783065 R.Wallis, D.A.Mitchell, R.Schmid, W.J.Schwaeble, and A.H.Keeble (2010).
Paths reunited: Initiation of the classical and lectin pathways of complement activation.
  Immunobiology, 215, 1.  
19473974 I.Bally, V.Rossi, T.Lunardi, N.M.Thielens, C.Gaboriaud, and G.J.Arlaud (2009).
Identification of the C1q-binding Sites of Human C1r and C1s: a refined three-dimensional model of the C1 complex of complement.
  J Biol Chem, 284, 19340-19348.  
19775369 X.Vallès, M.R.Sarrias, F.Casals, M.Farnós, R.Piñer, B.Suárez, L.Morais, I.Mandomando, B.Sigaúque, A.Roca, P.L.Alonso, A.Torres, N.M.Thielens, and F.Lozano (2009).
Genetic and structural analysis of MBL2 and MASP2 polymorphisms in south-eastern African children.
  Tissue Antigens, 74, 298-307.  
18177377 R.Pagh, K.Duus, I.Laursen, P.R.Hansen, J.Mangor, N.Thielens, G.J.Arlaud, L.Kongerslev, P.Højrup, and G.Houen (2008).
The chaperone and potential mannan-binding lectin (MBL) co-receptor calreticulin interacts with MBL through the binding site for MBL-associated serine proteases.
  FEBS J, 275, 515-526.  
17989695 B.A.Appleton, P.Wu, J.Maloney, J.Yin, W.C.Liang, S.Stawicki, K.Mortara, K.K.Bowman, J.M.Elliott, W.Desmarais, J.F.Bazan, A.Bagri, M.Tessier-Lavigne, A.W.Koch, Y.Wu, R.J.Watts, and C.Wiesmann (2007).
Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding.
  EMBO J, 26, 4902-4912.
PDB codes: 2qqi 2qqj 2qqk 2qql 2qqm 2qqn 2qqo
17544814 R.Wallis (2007).
Interactions between mannose-binding lectin and MASPs during complement activation by the lectin pathway.
  Immunobiology, 212, 289-299.  
17252003 S.Thiel, R.Steffensen, I.J.Christensen, W.K.Ip, Y.L.Lau, I.J.Reason, H.Eiberg, M.Gadjeva, M.Ruseva, and J.C.Jensenius (2007).
Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms.
  Genes Immun, 8, 154-163.  
15948998 C.Stover, S.Barrett, N.J.Lynch, J.N.Barker, D.Burden, R.Trembath, W.Schwaeble, and C.Veal (2005).
Functional MASP2 single nucleotide polymorphism plays no role in psoriasis.
  Br J Dermatol, 152, 1313-1315.  
16262703 M.A.Campanero-Rhodes, M.Menéndez, J.L.Sáiz, L.Sanz, J.J.Calvete, and D.Solís (2005).
Analysis of the stability of the spermadhesin PSP-I/PSP-II heterodimer. Effects of Zn2+ and acidic pH.
  FEBS J, 272, 5663-5670.  
16252250 R.L.Rich, and D.G.Myszka (2005).
Survey of the year 2004 commercial optical biosensor literature.
  J Mol Recognit, 18, 431-478.  
16189649 R.Sørensen, S.Thiel, and J.C.Jensenius (2005).
Mannan-binding-lectin-associated serine proteases, characteristics and disease associations.
  Springer Semin Immunopathol, 27, 299-319.  
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.