PDBsum entry: 1qqk

Hormone/growth factor

PDB-id

1qqk


	Biological unit* = asymmetric unit, as shown (as deduced by PQS*)

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Description

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Protein chains

Waters ×128

* Residue conservation analysis

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PDB id:

1qqk

Name:

Hormone/growth factor

Title:

The crystal structure of fibroblast growth factor 7 (keratinocyte growth factor)

Structure:

Fibroblast growth factor 7. Chain: a, b. Fragment: fgf-7beta (ser-54). Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: prostate. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biological unit:

Dimer (from PQS)

UniProt:

Chains A, B: Q02195 (FGF7_RAT)

Seq:

194 a.a.

Struc:

129 a.a.*

Key:		PfamA domain			PfamB domain
		Secondary structure			CATH domain

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Resolution:

3.10Å

R-factor:

0.233

R-free:

0.324

Authors:

S.Ye,Y.Luo,H.Pelletier,W.L.Mckeehan

Key ref:

S.Ye et al. (2001). Structural basis for interaction of FGF-1, FGF-2, and FGF-7 with different heparan sulfate motifs.. Biochemistry, 40, 14429-14439. [PubMed id: 11724555] [DOI: 10.1021/bi011000u]

Date:

07-Jun-99

Release date:

14-Jan-00

Related entries:

1qql
fibroblast growth factor 7/1 chimera

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Key reference

DOI no: 10.1021/bi011000u Biochemistry 40:14429-14439 (2001)

PubMed id: 11724555

Structural basis for interaction of FGF-1, FGF-2, and FGF-7 with different heparan sulfate motifs.

S.Ye, Y.Luo, W.Lu, R.B.Jones, R.J.Linhardt, I.Capila, T.Toida, M.Kan, H.Pelletier, W.L.McKeehan.

ABSTRACT

Stromal cell-derived FGF-7 binds and activates only the resident FGFR2IIIb in epithelial cells while FGF-1 and FGF-2 exhibit a broader interaction with multiple isoforms of FGFR. Here we report the structure of FGF-7 that has been solved to 3.1 A resolution by molecular replacement with the structure of a dual function chimera of FGF-7 and FGF-1 (FGF-7/1) which was resolved to 2.3 A. Comparison of the FGF-7 structure to that of FGF-1 and FGF-2 revealed the strongly conserved Calpha backbone among the three FGF polypeptides and the surface hydrophobic patch that forms the primary receptor-binding domain. In contrast, a decrease and dispersion of the positive surface charge density characterized the heparin-binding domain of FGF-7 defined by homology to that of FGF-1 and FGF-2 in complexes with heparin. A simple heparin hexasaccharide that cocrystallized with FGF-1 and FGF-2 and protected both against protease in solution failed to exhibit the same properties with FGF-7. In contrast to FGF-1 and FGF-2, protection of FGF-7 was enhanced by heparin oligosaccharides of increased length with those exhibiting a 3-O-sulfate being the most effective. Protection of FGF-7 required interaction with specifically the fraction of crude heparin retained on antithrombin affinity columns. Conversely, heparin enriched by affinity for immobilized FGF-7 exhibited anti-factor Xa activity similar to that purified on an antithrombin affinity matrix. In contrast, an FGF-1 affinity matrix enriched the fraction of crude heparin with low anti-factor Xa activity. The results provide a structural basis to suggest that the unique FGF-7 heparin-binding (HB) domain underlies a specific restriction in respect to composition and length of the heparan sulfate motif that may impact specificity of localization, stability, and trafficking of FGF-7 in the microenvironment, and formation and activation of the FGFR2IIIb kinase signaling complex in epithelial cells.

Literature references that cite this PDB file's key reference

PubMed id Reference

19387498 S.Peterson, A.Frick, and J.Liu (2009).
Design of biologically active heparan sulfate and heparin using an enzyme-based approach.

Nat Prod Rep, 26, 610-627.

18669628 A.I.de Agostini, J.C.Dong, C.de Vantéry Arrighi, M.A.Ramus, I.Dentand-Quadri, S.Thalmann, P.Ventura, V.Ibecheole, F.Monge, A.M.Fischer, S.HajMohammadi, N.W.Shworak, L.Zhang, Z.Zhang, and R.J.Linhardt (2008).
Human follicular fluid heparan sulfate contains abundant 3-O-sulfated chains with anticoagulant activity.

J Biol Chem, 283, 28115-28124.

18288776 A.Liang, X.Liu, Y.Du, K.Wang, and B.Lin (2008).
Further characterization of the binding of heparin to granulocyte colony-stimulating factor: importance of sulfate groups.

Electrophoresis, 29, 1286-1290.

17339340 R.Goetz, A.Beenken, O.A.Ibrahimi, J.Kalinina, S.K.Olsen, A.V.Eliseenkova, C.Xu, T.A.Neubert, F.Zhang, R.J.Linhardt, X.Yu, K.E.White, T.Inagaki, S.A.Kliewer, M.Yamamoto, H.Kurosu, Y.Ogawa, M.Kuro-o, B.Lanske, M.S.Razzaque, and M.Mohammadi (2007).
Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members.

Mol Cell Biol, 27, 3417-3428.

PDB codes: 2p23 2p39

17094125 T.Derrick, A.O.Grillo, S.N.Vitharana, L.Jones, J.Rexroad, A.Shah, M.Perkins, T.M.Spitznagel, and C.R.Middaugh (2007).
Effect of polyanions on the structure and stability of repifermin (keratinocyte growth factor-2).

J Pharm Sci, 96, 761-776.

17525467 T.J.Kamerzell, S.B.Joshi, D.McClean, L.Peplinskie, K.Toney, D.Papac, M.Li, and C.R.Middaugh (2007).
Parathyroid hormone is a heparin/polyanion binding protein: binding energetics and structure modification.

Protein Sci, 16, 1193-1203.

16834555 R.Sasisekharan, R.Raman, and V.Prabhakar (2006).
Glycomics approach to structure-function relationships of glycosaminoglycans.

Annu Rev Biomed Eng, 8, 181-231.

16929488 X.Huang, C.Yu, C.Jin, C.Yang, R.Xie, D.Cao, F.Wang, and W.L.McKeehan (2006).
Forced expression of hepatocyte-specific fibroblast growth factor 21 delays initiation of chemically induced hepatocarcinogenesis.

Mol Carcinog, 45, 934-942.

16728399 Y.Luo, S.Ye, M.Kan, and W.L.McKeehan (2006).
Control of fibroblast growth factor (FGF) 7- and FGF1-induced mitogenesis and downstream signaling by distinct heparin octasaccharide motifs.

J Biol Chem, 281, 21052-21061.

16315317 Y.Luo, S.Ye, M.Kan, and W.L.McKeehan (2006).
Structural specificity in a FGF7-affinity purified heparin octasaccharide required for formation of a complex with FGF7 and FGFR2IIIb.

J Cell Biochem, 97, 1241-1258.

16107334 E.P.Girardin, S.Hajmohammadi, B.Birmele, A.Helisch, N.W.Shworak, and A.I.de Agostini (2005).
Synthesis of anticoagulantly active heparan sulfate proteoglycans by glomerular epithelial cells involves multiple 3-O-sulfotransferase isoforms and a limiting precursor pool.

J Biol Chem, 280, 38059-38070.

14694431 B.Berisha, F.Sinowatz, and D.Schams (2004).
Expression and localization of fibroblast growth factor (FGF) family members during the final growth of bovine ovarian follicles.

Mol Reprod Dev, 67, 162-171.

12591959 B.K.Yeh, M.Igarashi, A.V.Eliseenkova, A.N.Plotnikov, I.Sher, D.Ron, S.A.Aaronson, and M.Mohammadi (2003).
Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors.

Proc Natl Acad Sci U S A, 100, 2266-2271.

PDB code: 1nun

12604799 R.Raman, G.Venkataraman, S.Ernst, V.Sasisekharan, and R.Sasisekharan (2003).
Structural specificity of heparin binding in the fibroblast growth factor family of proteins.

Proc Natl Acad Sci U S A, 100, 2357-2362.

14502551 Y.Luo, H.H.Cho, and W.L.McKeehan (2003).
Biospecific extraction and neutralization of anticoagulant heparin with fibroblast growth factors (FGF).

J Pharm Sci, 92, 2117-2127.

12138164 G.Xia, J.Chen, V.Tiwari, W.Ju, J.P.Li, A.Malmstrom, D.Shukla, and J.Liu (2002).
Heparan sulfate 3-O-sulfotransferase isoform 5 generates both an antithrombin-binding site and an entry receptor for herpes simplex virus, type 1.

J Biol Chem, 277, 37912-37919.

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 codes are shown on the right.