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Titolo:
Structure and stability effects of mutations designed to increase the primary sequence symmetry within the core region of a beta-trefoil
Autore:
Brych, SR; Blaber, SI; Logan, TM; Blaber, M;
Indirizzi:
Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA Florida State Univ Tallahassee FL USA 32306 ys, Tallahassee, FL 32306 USA Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA FloridaState Univ Tallahassee FL USA 32306 em, Tallahassee, FL 32306 USA
Titolo Testata:
PROTEIN SCIENCE
fascicolo: 12, volume: 10, anno: 2001,
pagine: 2587 - 2599
SICI:
0961-8368(200112)10:12<2587:SASEOM>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
FIBROBLAST-GROWTH-FACTOR; SHEET PROTEIN INTERLEUKIN-1-BETA; CRYSTAL-STRUCTURE; BACTERIOPHAGE-T4 LYSOZYME; TRYPSIN-INHIBITOR; T4 LYSOZYME; ERYTHRINA-CAFFRA; PORCINE TRYPSIN; RESOLUTION; REFINEMENT;
Keywords:
beta-trefoil; fibroblast growth factor; core-packing; protein engineering; protein evolution;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
69
Recensione:
Indirizzi per estratti:
Indirizzo: Blaber, M Florida State Univ, Inst Mol Biophys, 201-MBB-4380, Tallahassee,FL 32306 USA Florida State Univ 201-MBB-4380 Tallahassee FL USA 32306 306 USA
Citazione:
S.R. Brych et al., "Structure and stability effects of mutations designed to increase the primary sequence symmetry within the core region of a beta-trefoil", PROTEIN SCI, 10(12), 2001, pp. 2587-2599

Abstract

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 ofFGF-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 1.0 Angstrom 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 thanstability, may contribute to the selective pressure for asymmetric primarycore sequences within symmetric protein architectures.

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Documento generato il 02/04/20 alle ore 02:51:03