1jt5
Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Terminal His Tag AND LEU 73 REPLACED BY VAL AND VAL 109 REPLACED BY LEU (L73V/V109L)
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OverviewOverview
Human acidic fibroblast growth factor (FGF-1) is a member of the, beta-trefoil hyperfamily and exhibits a characteristic threefold symmetry, of the tertiary structure. However, evidence of this symmetry is not, readily apparent at the level of the primary sequence. This suggests that, while selective pressures may exist to retain (or converge upon) a, symmetric tertiary structure, other selective pressures have resulted in, divergence of the primary sequence during evolution. Using intra-chain and, homologue sequence comparisons for 19 members of this family of proteins, we have designed mutants of FGF-1 that constrain a subset of core-packing, residues to threefold symmetry at the level of the primary sequence. The, consequences of these mutations regarding structure and stability were, evaluated using a combination of X-ray crystallography and differential, scanning calorimetry. The mutational effects on structure and stability, can be rationalized through the characterization of "microcavities" within, the core detected using a 1.0A probe radius. The results show that the, symmetric constraint within the primary sequence is compatible with a, well-packed core and near wild-type stability. However, despite the, general maintenance of overall thermal stability, a noticeable increase in, non-two-state denaturation follows the increase in primary sequence, symmetry. Therefore, properties of folding, rather than stability, may, contribute to the selective pressure for asymmetric primary core sequences, within symmetric protein architectures.
DiseaseDisease
Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[602115], LADD syndrome OMIM:[602115]
About this StructureAbout this Structure
1JT5 is a Single protein structure of sequence from Homo sapiens with SO4 as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structure and stability effects of mutations designed to increase the primary sequence symmetry within the core region of a beta-trefoil., Brych SR, Blaber SI, Logan TM, Blaber M, Protein Sci. 2001 Dec;10(12):2587-99. PMID:11714927
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