PDBsum entry 2aqz

Hormone/growth factor

PDB id: 2aqz

Contents

Protein chains

140 a.a. *

Ligands

SO4

Waters ×277

* Residue conservation analysis

PDB id:

2aqz

Name:

Hormone/growth factor

Title:

Crystal structure of fgf-1, s17t/n18t/g19 deletion mutant

Structure:

Heparin-binding growth factor 1. Chain: a, b. Synonym: hbgf-1, acidic fibroblast growth factor, afgf, beta- endothelial cell growth factor, ecgf- beta. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fgf1, fgfa. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.85Å R-factor: 0.196 R-free: 0.226

Authors:

J.Lee,M.Blaber

Key ref:

J.Lee et al. (2006). Conversion of type I 4:6 to 3:5 beta-turn types in human acidic fibroblast growth factor: effects upon structure, stability, folding, and mitogenic function. Proteins, 62, 686-697. PubMed id: 16355415 DOI: 10.1002/prot.20808

Date:

18-Aug-05 Release date: 07-Feb-06

Protein chains

P05230  (FGF1_HUMAN) -  Fibroblast growth factor 1 from Homo sapiens

Seq: 155 a.a.

Struc: 140 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1002/prot.20808

Proteins 62:686-697 (2006)

PubMed id: 16355415

Conversion of type I 4:6 to 3:5 beta-turn types in human acidic fibroblast growth factor: effects upon structure, stability, folding, and mitogenic function.

J.Lee, V.K.Dubey, T.Somasundaram, M.Blaber.

ABSTRACT

Human acidic fibroblast growth factor (FGF-1) is a member of the beta-trefoil superfold, a protein architecture that exhibits a characteristic threefold axis of structural symmetry. FGF-1 contains 11 beta-turns, the majority being type I 3:5; however, a type I 4:6 turn is also found at three symmetry-related locations. The relative uniqueness of the type I 4:6 turn in the FGF-1 structure suggests it may play a key role in the stability, folding, or function of the protein. To test this hypothesis a series of deletion mutations were constructed, the aim of which was to convert existing type I 4:6 turns at two locations into type I 3:5 turns. The results show it is possible to successfully substitute the type I 4:6 turn by a type I 3:5 turn with minimal impact upon protein stability or folding. Thus, these different turn structures, even though they differ in length, exhibit similar energetic properties. Additional sequence swapping mutations within the introduced type I 3:5 turns suggests that the turn sequence primarily affects stability but not turn structure (which appears dictated primarily by the local environment). Although the results suggest that a stable, foldable beta-trefoil protein may be designed utilizing a single turn type (type I 3:5), a type I 4:6 turn at turn 1 of FGF-1 appears essential for efficient mitogenic function.

Selected figure(s)

Figure 2.
Figure 2. (Upper panel) Relaxed stereodiagram of an overlay of the turn 1 region in the wild-type FGF-1 structure (light gray) with that of the G19 mutant (dark gray). Also shown is a 2F[o] - F[c] difference electron density map of the G19 mutant contoured at 1.5 . Turn 1 has converted from type I 4:6 in the wild-type structure to a type I 3:5 in the G19 mutant. (Middle panel) Relaxed stereodiagram of an overlay of the turn 5 region in the wild-type FGF-1 structure (light gray) with that of the E60 mutant (dark gray). Also shown is a 2F[o] - F[c] difference electron density map of the E60 mutant contoured at 1.5 . Turn 5 has converted from type I 4:6 in the wild-type structure to a type I 3:5 in the E60 mutant. (Lower panel) Relaxed stereodiagram of an overlay of the turn 1 region in the G19 mutant structure (light gray) with that of the S17T/N18T/ G19 mutant (dark gray). Also shown is a 2F[o] - F[c] difference electron density map of the S17T/N18T/ G19 mutant contoured at 1.5 . The S17T/N18T mutations in the turn 1 region are accommodated with essentially no change to the turn structure in the G19 mutant background.

Figure 5.
Figure 5. (Upper panel) Relaxed stereodiagram of an overlay of the turn 1 (CPK color scheme) and turn 5 (gray) regions in wild-type FGF-1 (PDB accession 1JQZ). (Lower panel) Relaxed stereo diagram of an overlay of the turn 1 (CPK color scheme) and turn 5 (gray) regions in the S17T/N18T/ G19 and E60 mutants, respectively. The structural similarity of these symmetry-related turns is retained as they are converted from type I 4:6 to type I 3:5 turns.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2006, 62, 686-697) copyright 2006.

Figures were selected by the author.