3O3Q

Crystal structure of "L44F/M67I/L73V/A103G/deletion 104-106/F108Y/V109L/L111I/C117V/R119G/deletion 120-122" mutant form of Human acidic fibroblast growth factor

Summary for 3O3Q

• Entry DOI: 10.2210/pdb3o3q/pdb
• Related: 1JQZ 3O49 3O4A 3O4B 3O4C 3O4D 3O4E
• Descriptor: Heparin-binding growth factor 1, GLYCEROL (3 entities in total)
• Functional Keywords: beta-trefoil, heparin-binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 63851.35

Authors

Lee, J.,Blaber, M. (deposition date: 2010-07-25, release date: 2011-02-23, Last modification date: 2023-09-06)

Primary citation

Lee, J.,Blaber, S.I.,Dubey, V.K.,Blaber, M.
A polypeptide "building block"top-down symmetric deconstruction".
J.Mol.Biol., 407:744-763, 2011

PubMed Abstract: Fibroblast growth factor-1, a member of the 3-fold symmetric β-trefoil fold, was subjected to a series of symmetric constraint mutations in a process termed "top-down symmetric deconstruction." The mutations enforced a cumulative exact 3-fold symmetry upon symmetrically equivalent positions within the protein and were combined with a stability screen. This process culminated in a β-trefoil protein with exact 3-fold primary-structure symmetry that exhibited excellent folding and stability properties. Subsequent fragmentation of the repeating primary-structure motif yielded a 42-residue polypeptide capable of spontaneous assembly as a homotrimer, producing a thermostable β-trefoil architecture. The results show that despite pronounced reduction in sequence complexity, pure symmetry in the design of a foldable, thermostable β-trefoil fold is possible. The top-down symmetric deconstruction approach provides a novel alternative means to successfully identify a useful polypeptide "building block" for subsequent "bottom-up" de novo design of target protein architecture.

PubMed: 21315087
DOI: 10.1016/j.jmb.2011.02.002

Experimental method

X-RAY DIFFRACTION (1.6 Å)