PDBsum entry 1rv6

Hormone/growth factor/receptor

PDB id

1rv6

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Contents

			Protein chains

					94 a.a. *


					92 a.a. *

			Ligands

					B3P

			Waters ×161

* Residue conservation analysis

PDB id:

1rv6

Links

Name:

Hormone/growth factor/receptor

Title:

Crystal structure of plgf in complex with domain 2 of vegfr1

Structure:

Placenta growth factor (plgf). Chain: v, w. Fragment: receptor binding domain. Engineered: yes. Flt1 protein. Chain: x, y. Fragment: domain-2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

Biol. unit:

Tetramer (from PQS)

Resolution:

2.45Å

R-factor:

0.198

R-free:

0.260

Authors:

H.W.Christinger,G.Fuh,A.M.De Vos,C.Wiesmann

Key ref:

H.W.Christinger et al. (2004). The crystal structure of placental growth factor in complex with domain 2 of vascular endothelial growth factor receptor-1. J Biol Chem, 279, 10382-10388. PubMed id: 14684734 DOI: 10.1074/jbc.M313237200

Date:

12-Dec-03

Release date:

20-Jan-04

PROCHECK

	Headers

	References

Protein chains

P49763 (PLGF_HUMAN) - Placenta growth factor from Homo sapiens

Seq: Struc:					221 a.a. 94 a.a.*

Protein chains

P17948 (VGFR1_HUMAN) - Vascular endothelial growth factor receptor 1 from Homo sapiens

Seq: Struc:

Seq: Struc:

Seq: Struc:					1338 a.a. 92 a.a.

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 2 residue positions (black crosses)



		Enzyme reactions

Enzyme class:

Chains X, Y: E.C.2.7.10.1 - receptor protein-tyrosine kinase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

L-tyrosyl-[protein]	+	ATP	=	O-phospho-L-tyrosyl-[protein]	+	ADP	+	H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1074/jbc.M313237200	J Biol Chem 279:10382-10388 (2004)
PubMed id: 14684734

The crystal structure of placental growth factor in complex with domain 2 of vascular endothelial growth factor receptor-1.
H.W.Christinger, G.Fuh, A.M.de Vos, C.Wiesmann.

ABSTRACT

Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family and plays an important role in pathological angiogenic events. PlGF exerts its biological activities through binding to VEGFR1, a receptor tyrosine kinase that consists of seven immunoglobulin-like domains in its extracellular portion. Here we report the crystal structure of PlGF bound to the second immunoglobulin-like domain of VEGFR1 at 2.5 A resolution and compare the complex to the closely related structure of VEGF bound to the same receptor domain. The two growth factors, PlGF and VEGF, share a sequence identity of approximately 50%. Despite this moderate sequence conservation, they bind to the same binding interface of VEGFR1 in a very similar fashion, suggesting that both growth factors could induce very similar if not identical signaling events.

Selected figure(s)



	Figure 5. FIG. 5. Sequence alignment of the PlGF and VEGF receptor-binding domain. Secondary structure elements are depicted at the top with dark gray arrows referring to -strands and light gray boxes to -helices. Numbers at top refer to human PlGF and numbers at bottom to human VEGF sequence. green, strictly conserved in all shown sequences; yellow, conserved in VEGF or PlGF only; orange, conserved among PlGF and among VEGF as different residues; bold font, monomer 1 receptor binding interface; bold font and underlined, monomer 2 receptor binding interface; boxed residues, core of receptor interface; italics, residues involved in dimer interface.		Figure 6. FIG. 6. Schematic representation of VEGF and PlGF homo- and heterodimers. A, PlGF homodimer; B, VEGF homodimer; C, PlGF/VEGF heterodimer. Note the asymmetric nature of the PlGF/VEGF heterodimer.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21510820

F.Boyaud, and N.Inguimbert (2011).
Soluble fms-like tyrosine kinase-1 antibody for diagnosis purposes (WO2010075475).

Expert Opin Ther Pat, 21, 971-975.

21148085

V.M.Leppänen, M.Jeltsch, A.Anisimov, D.Tvorogov, K.Aho, N.Kalkkinen, P.Toivanen, S.Ylä-Herttuala, K.Ballmer-Hofer, and K.Alitalo (2011).
Structural determinants of vascular endothelial growth factor-D receptor binding and specificity.

Blood, 117, 1507-1515.

PDB code:

2xv7

20564033

R.Di Stasi, D.Diana, D.Capasso, R.Palumbo, A.Romanelli, C.Pedone, R.Fattorusso, and L.D.D'Andrea (2010).
VEGFR1(D2) in drug discovery: Expression and molecular characterization.

Biopolymers, 94, 800-809.

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

19658168

E.Stuttfeld, and K.Ballmer-Hofer (2009).
Structure and function of VEGF receptors.

IUBMB Life, 61, 915-922.

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.

19387974

V.Goncalves, B.Gautier, F.Huguenot, P.Leproux, C.Garbay, M.Vidal, and N.Inguimbert (2009).
Total chemical synthesis of the D2 domain of human VEGF receptor 1.

J Pept Sci, 15, 417-422.

18184864

S.Soro, A.Orecchia, L.Morbidelli, P.M.Lacal, V.Morea, K.Ballmer-Hofer, F.Ruffini, M.Ziche, S.D'Atri, G.Zambruno, A.Tramontano, and C.M.Failla (2008).
A proangiogenic peptide derived from vascular endothelial growth factor receptor-1 acts through alpha5beta1 integrin.

Blood, 111, 3479-3488.

17293873

C.Ruch, G.Skiniotis, M.O.Steinmetz, T.Walz, and K.Ballmer-Hofer (2007).
Structure of a VEGF-VEGF receptor complex determined by electron microscopy.

Nat Struct Mol Biol, 14, 249-250.

17187248

N.Miyamoto, Y.de Kozak, J.C.Jeanny, A.Glotin, F.Mascarelli, P.Massin, D.BenEzra, and F.Behar-Cohen (2007).
Placental growth factor-1 and epithelial haemato-retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy.

Diabetologia, 50, 461-470.

16633338

A.K.Olsson, A.Dimberg, J.Kreuger, and L.Claesson-Welsh (2006).
VEGF receptor signalling - in control of vascular function.

Nat Rev Mol Cell Biol, 7, 359-371.

16672228

M.Pieren, A.E.Prota, C.Ruch, D.Kostrewa, A.Wagner, K.Biedermann, F.K.Winkler, and K.Ballmer-Hofer (2006).
Crystal structure of the Orf virus NZ2 variant of vascular endothelial growth factor-E. Implications for receptor specificity.

J Biol Chem, 281, 19578-19587.

PDB code:

2gnn

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.

15693956

D.I.Holmes, and I.Zachary (2005).
The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease.

Genome Biol, 6, 209.

16252250

R.L.Rich, and D.G.Myszka (2005).
Survey of the year 2004 commercial optical biosensor literature.

J Mol Recognit, 18, 431-478.

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.