3FJJ

Crystal structure of C83V mutant of Human acidic fibroblast growth factor

Summary for 3FJJ

• Entry DOI: 10.2210/pdb3fjj/pdb
• Related: 1JQZ 3FGM 3FJ8 3FJ9 3FJA 3FJB 3FJC 3FJD 3FJE 3FJF 3FJH 3FJI 3FJK 3HOM
• Descriptor: Heparin-binding growth factor 1, SULFATE ION, FORMIC ACID, ... (4 entities in total)
• Functional Keywords: beta-trefoil, acetylation, angiogenesis, developmental protein, differentiation, growth factor, heparin-binding, mitogen, polymorphism, hormone
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P05230
• Total number of polymer chains: 2
• Total formula weight: 33737.69

Authors

Blaber, M.,Lee, J. (deposition date: 2008-12-14, release date: 2009-10-06, Last modification date: 2023-09-06)

Primary citation

Lee, J.,Blaber, M.
Structural basis of conserved cysteine in the fibroblast growth factor family: evidence for a vestigial half-cystine.
J.Mol.Biol., 393:128-139, 2009

PubMed 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.

PubMed: 19683004
DOI: 10.1016/j.jmb.2009.08.007

Experimental method

X-RAY DIFFRACTION (1.9 Å)