spacer
spacer

PDBsum entry 1fzv

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Hormone/growth factor PDB id
1fzv
Jmol
Contents
Protein chain
100 a.a. *
Ligands
MPD ×2
Waters ×132
* Residue conservation analysis
PDB id:
1fzv
Name: Hormone/growth factor
Title: The crystal structure of human placenta growth factor-1 (plgf-1), an angiogenic protein at 2.0a resolution
Structure: Placenta growth factor. Chain: a, b. Synonym: plgf-1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: placenta. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.216     R-free:   0.247
Authors: S.Iyer,D.D.Leonidas,G.J.Swaminathan,D.Maglione,M.Battisti, M.Tucci,M.G.Persico,K.R.Acharya
Key ref:
S.Iyer et al. (2001). The crystal structure of human placenta growth factor-1 (PlGF-1), an angiogenic protein, at 2.0 A resolution. J Biol Chem, 276, 12153-12161. PubMed id: 11069911 DOI: 10.1074/jbc.M008055200
Date:
04-Oct-00     Release date:   09-May-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P49763  (PLGF_HUMAN) -  Placenta growth factor
Seq:
Struc:
221 a.a.
100 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biochemical function     growth factor activity     1 term  

 

 
DOI no: 10.1074/jbc.M008055200 J Biol Chem 276:12153-12161 (2001)
PubMed id: 11069911  
 
 
The crystal structure of human placenta growth factor-1 (PlGF-1), an angiogenic protein, at 2.0 A resolution.
S.Iyer, D.D.Leonidas, G.J.Swaminathan, D.Maglione, M.Battisti, M.Tucci, M.G.Persico, K.R.Acharya.
 
  ABSTRACT  
 
The angiogenic molecule placenta growth factor (PlGF) is a member of the cysteine-knot family of growth factors. In this study, a mature isoform of the human PlGF protein, PlGF-1, was crystallized as a homodimer in the crystallographic asymmetric unit, and its crystal structure was elucidated at 2.0 A resolution. The overall structure of PlGF-1 is similar to that of vascular endothelial growth factor (VEGF) with which it shares 42% amino acid sequence identity. Based on structural and biochemical data, we have mapped several important residues on the PlGF-1 molecule that are involved in recognition of the fms-like tyrosine kinase receptor (Flt-1, also known as VEGFR-1). We propose a model for the association of PlGF-1 and Flt-1 domain 2 with precise shape complementarity, consider the relevance of this assembly for PlGF-1 signal transduction, and provide a structural basis for altered specificity of this molecule.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Structural comparison of PlGF-1 and other members of the cysteine-knot super family. A, representation of the PlGF-1 homodimer structure. Disulfide bonds are shown in a ball-and-stick representation. The inset presents the organization of three intra- (in yellow) and one interdisulfide bridge (in green) in the cysteine-knot motif. Each monomer in the homodimer is colored differently to enhance clarity. Orange, monomer A; cyan, monomer B. B, representatives of known structures from the cysteine-knot protein family of dimeric molecules. a, VEGF (PDB code 2VPF, Ref. 39); b, PDGF-BB (PDB code 1PDG, Ref. 51); c, TGF- 2 (PDB code 1TFG, Ref. 52); and d, NGF (PDB code 1BTG, Ref. 53). With the exception of NGF, the homodimer 2-fold axis is perpendicular to the plane of the -sheet. The cysteine knots are highlighted. C, structure-based sequence alignment of PlGF-1 with VEGF (38, 39). Amino acid residues that form part of the secondary structural elements ( -strands and helices) as determined by DSSP (60) are shown in blue and red, respectively. The cysteine residues are shaded pink. VEGF residues involved in Flt-1 (VEGFR-1) binding (40), and the equivalent residues in PlGF-1 (based on a modeling study) are boxed and shaded in yellow. The conserved glycine residue in both structures is underlined. This figure was created with the program ALSCRIPT (61). D, stereo view displaying the C traces of PlGF-1 (orange) and VEGF (cyan) (39) homodimers after alignment of the two structures with the program "O" (49). A, B, and D were created with the program MOLSCRIPT (59).
Figure 2.
Fig. 2. Proposed model for the PlGF-1·Flt-1[D2] complex based on the crystal structures of PlGF-1 (present study) and the VEGF·Flt-1[D2] complex (40), PDB accession code 1FLT. A, PlGF-1 homodimer is shown in orange (molecule A) and cyan (molecule B), whereas the Flt-1[D2] molecules are shown in purple and green. B, stereo views of contact residues (C atoms plus sidechain atoms) at the putative PlGF-1·Flt-1[D2] interface. Residues from PlGF-1 monomers A and B are marked in orange and cyan, respectively. Residues from Flt-1 (figure based on model shown in A) are colored in green. The sidechains for Glu73 and Asn74 in free PlGF-1 are disordered and hence are treated as alanines. C, stereo views of contact residues (C atoms plus sidechain atoms) for PlGF-1. Residues from monomer A and B are marked in orange and cyan, respectively (figure based on model shown in A). The sidechains for Glu73 and Asn74 in free PlGF-1 are disordered and hence are treated as alanines. D, stereo views of contact residues (C atoms plus sidechain atoms) for Flt-1[D2] (figure based on model shown in A). E, stereo views showing the location of the groove in PlGF-1 (residues Asp72, Glu73, Val52, Met55, Val45, Asp43, and Ser59) and VEGF (Asp63, Glu64, Ile^43, Ile^46, Phe^36, Asp34, and Ser50), implicated for recognition of domain 3 of Flt-1 (40). The figure also shows the difference in conformation for segment 90-95 in PlGF-1 and 81-86 in VEGF. Residues Ile^83, Lys84, and Pro85 are implicated in KDR recognition in VEGF (38), and the corresponding residues in PlGF-1 are Ile^92, Ser94, and Arg93. The sidechains for PIGF-1 and VEGF are shown in orange and cyan, respectively. Ser94 and Glu73 in the PlGF-1 structure are represented as alanines because of insufficient electron density beyond the C atom. A-E was generated using MOLSCRIPT (59).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 12153-12161) copyright 2001.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20935166 E.Kaza, K.Ablasser, D.Poutias, E.R.Griffiths, F.A.Saad, J.G.Hofstaetter, P.J.del Nido, and I.Friehs (2011).
Up-regulation of soluble vascular endothelial growth factor receptor-1 prevents angiogenesis in hypertrophied myocardium.
  Cardiovasc Res, 89, 410-418.  
  21401353 O.Zakiyanov, M.Kalousová, T.Zima, and V.Tesaƙ (2011).
Placental growth factor in patients with decreased renal function.
  Ren Fail, 33, 291-297.  
20501651 S.Iyer, P.I.Darley, and K.R.Acharya (2010).
Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity.
  J Biol Chem, 285, 23779-23789.
PDB code: 2xac
20145116 V.M.Leppänen, A.E.Prota, M.Jeltsch, A.Anisimov, N.Kalkkinen, T.Strandin, H.Lankinen, A.Goldman, K.Ballmer-Hofer, and K.Alitalo (2010).
Structural determinants of growth factor binding and specificity by VEGF receptor 2.
  Proc Natl Acad Sci U S A, 107, 2425-2430.
PDB codes: 2x1w 2x1x
19443835 A.Anisimov, A.Alitalo, P.Korpisalo, J.Soronen, S.Kaijalainen, V.M.Leppänen, M.Jeltsch, S.Ylä-Herttuala, and K.Alitalo (2009).
Activated forms of VEGF-C and VEGF-D provide improved vascular function in skeletal muscle.
  Circ Res, 104, 1302-1312.  
19207011 H.Q.Hu, Y.N.Sun, S.P.Luo, Q.Zhou, F.L.Tao, Z.Chen, Y.Xu, and Q.Zhou (2009).
Generation of a mouse monoclonal antibody recognizing both the native and denatured forms of human VEGF.
  Hybridoma (Larchmt), 28, 51-57.  
19366703 P.I.Toivanen, T.Nieminen, L.Viitanen, A.Alitalo, M.Roschier, S.Jauhiainen, J.E.Markkanen, O.H.Laitinen, T.T.Airenne, T.A.Salminen, M.S.Johnson, K.J.Airenne, and S.Ylä-Herttuala (2009).
Novel vascular endothelial growth factor D variants with increased biological activity.
  J Biol Chem, 284, 16037-16048.  
18568405 D.Ribatti (2008).
The discovery of the placental growth factor and its role in angiogenesis: a historical review.
  Angiogenesis, 11, 215-221.  
18922791 S.Ponticelli, D.Marasco, V.Tarallo, R.J.Albuquerque, S.Mitola, A.Takeda, J.M.Stassen, M.Presta, J.Ambati, M.Ruvo, and S.De Falco (2008).
Modulation of angiogenesis by a tetrameric tripeptide that antagonizes vascular endothelial growth factor receptor 1.
  J Biol Chem, 283, 34250-34259.  
16751784 C.K.Min, S.Y.Kim, M.J.Lee, K.S.Eom, Y.J.Kim, H.J.Kim, S.Lee, S.G.Cho, D.W.Kim, J.W.Lee, W.S.Min, C.C.Kim, and C.S.Cho (2006).
Vascular endothelial growth factor (VEGF) is associated with reduced severity of acute graft-versus-host disease and nonrelapse mortality after allogeneic stem cell transplantation.
  Bone Marrow Transplant, 38, 149-156.  
  16711023 H.Shen, H.Liu, H.Chen, Y.Guo, M.Zhang, X.Xu, and W.Xiang (2006).
Analysis of placental growth factor in placentas of normal pregnant women and women with hypertensive disorders of pregnancy.
  J Huazhong Univ Sci Technolog Med Sci, 26, 116-119.  
16465447 S.Cébe-Suarez, A.Zehnder-Fjällman, and K.Ballmer-Hofer (2006).
The role of VEGF receptors in angiogenesis; complex partnerships.
  Cell Mol Life Sci, 63, 601-615.  
16972015 Y.Yamazaki, and T.Morita (2006).
Molecular and functional diversity of vascular endothelial growth factors.
  Mol Divers, 10, 515-527.  
16279938 L.J.Reigstad, J.E.Varhaug, and J.R.Lillehaug (2005).
Structural and functional specificities of PDGF-C and PDGF-D, the novel members of the platelet-derived growth factors family.
  FEBS J, 272, 5723-5741.  
  15212678 D.S.Torry, M.Hinrichs, and R.J.Torry (2004).
Determinants of placental vascularity.
  Am J Reprod Immunol, 51, 257-268.  
15197767 P.An, H.Lei, J.Zhang, S.Song, L.He, G.Jin, X.Liu, J.Wu, L.Meng, M.Liu, and C.Shou (2004).
Suppression of tumor growth and metastasis by a VEGFR-1 antagonizing peptide identified from a phage display library.
  Int J Cancer, 111, 165-173.  
12871269 M.Autiero, A.Luttun, M.Tjwa, and P.Carmeliet (2003).
Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders.
  J Thromb Haemost, 1, 1356-1370.  
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.