spacer
spacer

PDBsum entry 3fji

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Hormone PDB id
3fji
Jmol
Contents
Protein chains
140 a.a. *
Ligands
SO4 ×2
Waters ×106
* Residue conservation analysis
PDB id:
3fji
Name: Hormone
Title: Crystal structure of k12v/c83i/c117v mutant of human acidic fibroblast growth factor
Structure: Heparin-binding growth factor 1. Chain: a, b, c, d. Synonym: hbgf-1, acidic fibroblast growth factor, afgf, beta-endothelial cell growth factor, ecgf-beta. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: fgf1, fgfa. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.55Å     R-factor:   0.212     R-free:   0.263
Authors: M.Blaber,J.Lee
Key ref:
J.Lee and M.Blaber (2009). Structural basis of conserved cysteine in the fibroblast growth factor family: evidence for a vestigial half-cystine. J Mol Biol, 393, 128-139. PubMed id: 19683004 DOI: 10.1016/j.jmb.2009.08.007
Date:
14-Dec-08     Release date:   06-Oct-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P05230  (FGF1_HUMAN) -  Fibroblast growth factor 1
Seq:
Struc:
155 a.a.
140 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   7 terms 
  Biological process     Fc-epsilon receptor signaling pathway   22 terms 
  Biochemical function     S100 protein binding     6 terms  

 

 
DOI no: 10.1016/j.jmb.2009.08.007 J Mol Biol 393:128-139 (2009)
PubMed id: 19683004  
 
 
Structural basis of conserved cysteine in the fibroblast growth factor family: evidence for a vestigial half-cystine.
J.Lee, M.Blaber.
 
  ABSTRACT  
 
The 22 members of the mouse/human fibroblast growth factor (FGF) family of proteins contain a conserved cysteine residue at position 83 (numbering scheme of the 140-residue form of FGF-1). Sequence and structure information suggests that this position is a free cysteine in 16 members and participates as a half-cystine in at least 3 (and perhaps as many as 6) other members. While a structural role as a half-cystine provides a stability basis for possible selective pressure, it is less clear why this residue is conserved as a free cysteine (although free buried thiols can limit protein functional half-life). To probe the structural role of the free cysteine at position 83 in FGF-1, we constructed Ala, Ser, Thr, Val, and Ile mutations and determined their effects on structure and stability. These results show that position 83 in FGF-1 is thermodynamically optimized to accept a free cysteine. A second cysteine mutation was introduced into wild-type FGF-1 at adjacent position Ala66, which is known to participate as a half-cystine with position 83 in FGF-8, FGF-19, and FGF-23. Results show that, unlike position 83, a free cysteine at position 66 destabilizes FGF-1; however, upon oxidation, a near-optimal disulfide bond is formed between Cys66 and Cys83, resulting in approximately 14 kJ/mol of increased thermostability. Thus, while the conserved free cysteine at position 83 in the majority of the FGF proteins may have a principal role in limiting functional half-life, evidence suggests that it is a vestigial half-cystine.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Relaxed stereo diagram of the X-ray crystal structures (molecule A in the asymmetric unit in each case) of position 83 mutants of FGF-1 (CPK coloring) showing the structural details adjacent to the site of mutation and overlaid with the coordinates of wild-type FGF-1 (PDB code 1JQZ; light gray). (a) Cys83 → Ala. (b) Cys83 → Ser. (c) Cys83 → Thr. (d) Cys83 → Val. (e) Cys83 → Ile.
Figure 3.
Fig. 3. Relaxed stereo diagram of the X-ray crystal structures of the reduced and oxidized forms of the Ala66 → Cys mutant (CPK coloring). (a) Molecule A in the asymmetric unit of reduced Ala66 → Cys overlaid with wild-type FGF-1 (PDB code 1JQZ; light gray). (b) Molecule B in the asymmetric unit of reduced Ala66 → Cys overlaid with wild-type FGF-1 (PDB code 1JQZ; light gray). (c) Molecule A of oxidized Ala66 → Cys overlaid with wild-type FGF-1 (PDB code 1JQZ; light gray). (d) Molecule A of oxidized Ala66 → Cys overlaid with FGF-23 (PDB code 2P39; light gray), which contains Cys at equivalent position Cys66 in FGF-1 and forms a disulfide with Cys at equivalent position Cys83.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2009, 393, 128-139) copyright 2009.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21173271 J.Lee, and M.Blaber (2011).
Experimental support for the evolution of symmetric protein architecture from a simple peptide motif.
  Proc Natl Acad Sci U S A, 108, 126-130.
PDB codes: 3o49 3o4a 3o4b 3o4c 3o4d 3ogf 3ol0
21315087 J.Lee, S.I.Blaber, V.K.Dubey, and M.Blaber (2011).
A polypeptide "building block" for the β-trefoil fold identified by "top-down symmetric deconstruction".
  J Mol Biol, 407, 744-763.
PDB code: 3o3q
21306635 S.Riazuddin, Z.M.Ahmed, R.S.Hegde, S.N.Khan, I.Nasir, U.Shaukat, S.Riazuddin, J.A.Butman, A.J.Griffith, T.B.Friedman, and B.Y.Choi (2011).
Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome.
  BMC Med Genet, 12, 21.  
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.