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PDBsum entry 2jyv

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protein links
Cytokine PDB id
2jyv
Jmol
Contents
Protein chain
32 a.a. *
* Residue conservation analysis
PDB id:
2jyv
Name: Cytokine
Title: Human granulin f
Structure: Granulin-2. Chain: a. Synonym: granulin f. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: grn. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 10 models
Authors: D.Tolkatchev,P.Wang,Z.Chen,P.Xu,F.Ni
Key ref:
D.Tolkatchev et al. (2008). Structure dissection of human progranulin identifies well-folded granulin/epithelin modules with unique functional activities. Protein Sci, 17, 711-724. PubMed id: 18359860 DOI: 10.1110/ps.073295308
Date:
19-Dec-07     Release date:   22-Apr-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P28799  (GRN_HUMAN) -  Granulins
Seq:
Struc:
 
Seq:
Struc:
593 a.a.
32 a.a.
Key:    PfamA domain  Secondary structure

 

 
DOI no: 10.1110/ps.073295308 Protein Sci 17:711-724 (2008)
PubMed id: 18359860  
 
 
Structure dissection of human progranulin identifies well-folded granulin/epithelin modules with unique functional activities.
D.Tolkatchev, S.Malik, A.Vinogradova, P.Wang, Z.Chen, P.Xu, H.P.Bennett, A.Bateman, F.Ni.
 
  ABSTRACT  
 
Progranulin is a secreted protein with important functions in several physiological and pathological processes, such as embryonic development, host defense, and wound repair. Autosomal dominant mutations in the progranulin gene cause frontotemporal dementia, while overexpression of progranulin promotes the invasive progression of a range of tumors, including those of the breast and the brain. Structurally, progranulin consists of seven-and-a-half tandem repeats of the granulin/epithelin module (GEM), several of which have been isolated as discrete 6-kDa GEM peptides. We have expressed all seven human GEMs using recombinant DNA in Escherichia coli. High-resolution NMR showed that only the three GEMs, hGrnA, hGrnC, and hGrnF, contain relatively well-defined three-dimensional structures in solution, while others are mainly mixtures of poorly structured disulfide isomers. The three-dimensional structures of hGrnA, hGrnC, and hGrnF contain a stable stack of two beta-hairpins in their N-terminal subdomains, but showed a more flexible C-terminal subdomain. Interestingly, of the well-structured GEMs, hGrnA demonstrated potent growth inhibition of a breast cancer cell line, while hGrnF was stimulatory. Poorly folded peptides were either weakly inhibitory or without activity. The functionally active and structurally well-characterized human hGrnA offers a unique opportunity for detailed structure-function studies of these important GEM proteins as novel members of mammalian growth factors.
 
  Selected figure(s)  
 
Figure 6.
Distribution of secondary structural elements in human granulins. (Arrows) Residues in [beta]-strand conformation. (Broken lines) Poorly defined regions (with a local average pairwise backbone RMSD >0.5 A based on tripeptide fragments with the residue in question as the central amino acid). [beta]-Hairpin loops and [beta]-turns are defined according to Sibanda and Thornton (1991).
Figure 7.
The clusters of the 10 lowest-energy human granulin structures superimposed using the backbone of the residues in structurally defined regions. Regions corresponding to the third [beta]-hairpin of cGrn1 (Hrabal et al. 1996) are consistently poorly defined and, for clarity of presentation, are not displayed. The N- and C-terminal fragments of hGrnA are superimposed over the backbone atoms of residues (2 --4, 7 --19, 23 --28) and (45 --49, 52 --57), respectively. The N- and C-terminal fragments of hGrnC1/hGrnC2 are superimposed over the backbone atoms of residues (6 --11, 14 --20, 22 --27) and (41 --58), respectively. HGrnF1 is superimposed over the backbone atoms of residues (2 --4, 8 --11, 14 --28).
 
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2008, 17, 711-724) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21511177 E.M.Moresco, and B.Beutler (2011).
Special delivery: granulin brings CpG DNA to Toll-like receptor 9.
  Immunity, 34, 453-455.  
21393509 W.Tang, Y.Lu, Q.Y.Tian, Y.Zhang, F.J.Guo, G.Y.Liu, N.M.Syed, Y.Lai, E.A.Lin, L.Kong, J.Su, F.Yin, A.H.Ding, A.Zanin-Zhorov, M.L.Dustin, J.Tao, J.Craft, Z.Yin, J.Q.Feng, S.B.Abramson, X.P.Yu, and C.J.Liu (2011).
The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice.
  Science, 332, 478-484.  
20026663 F.Yin, R.Banerjee, B.Thomas, P.Zhou, L.Qian, T.Jia, X.Ma, Y.Ma, C.Iadecola, M.F.Beal, C.Nathan, and A.Ding (2010).
Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice.
  J Exp Med, 207, 117.  
20415586 K.Sleegers, M.Cruts, and C.Van Broeckhoven (2010).
Molecular pathways of frontotemporal lobar degeneration.
  Annu Rev Neurosci, 33, 71-88.  
20653509 V.N.Uversky (2010).
Targeting intrinsically disordered proteins in neurodegenerative and protein dysfunction diseases: another illustration of the D(2) concept.
  Expert Rev Proteomics, 7, 543-564.  
  20489155 W.X.Wang, B.R.Wilfred, S.K.Madathil, G.Tang, Y.Hu, J.Dimayuga, A.J.Stromberg, Q.Huang, K.E.Saatman, and P.T.Nelson (2010).
miR-107 regulates granulin/progranulin with implications for traumatic brain injury and neurodegenerative disease.
  Am J Pathol, 177, 334-345.  
19795409 A.Bateman, and H.P.Bennett (2009).
The granulin gene family: from cancer to dementia.
  Bioessays, 31, 1245-1254.  
19056610 B.S.Youn, S.I.Bang, N.Klöting, J.W.Park, N.Lee, J.E.Oh, K.B.Pi, T.H.Lee, K.Ruschke, M.Fasshauer, M.Stumvoll, and M.Blüher (2009).
Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue.
  Diabetes, 58, 627-636.  
19816559 M.J.Smout, T.Laha, J.Mulvenna, B.Sripa, S.Suttiprapa, A.Jones, P.J.Brindley, and A.Loukas (2009).
A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells.
  PLoS Pathog, 5, e1000611.  
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.