FIBROBLAST GROWTH FACTOR
成纤维细胞生长因子
基本信息
- 批准号:8363337
- 负责人:
- 金额:$ 0.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-07-01 至 2012-06-30
- 项目状态:已结题
- 来源:
- 关键词:ArchitectureCharacteristicsCrystallographyDNA Sequencing FacilityDifferential Scanning CalorimetryEvolutionExhibitsFamily memberFibroblast Growth Factor 1FundingGrantHomologous GeneHumanLightMaintenanceMutationNational Center for Research ResourcesPrincipal InvestigatorPropertyProtein FamilyProteinsRadialResearchResearch InfrastructureResourcesSourceStructureSynchrotronsTrefoilUnited States National Institutes of HealthX-Ray Crystallographycostdesignmembermutantpressure
项目摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
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.
该子项目是利用资源的众多研究子项目之一
由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持
并且子项目的主要研究者可能是由其他来源提供的,
包括其他 NIH 来源。 子项目可能列出的总成本
代表子项目使用的中心基础设施的估计数量,
NCRR 赠款不直接向子项目或子项目工作人员提供资金。
人酸性成纤维细胞生长因子 (FGF-1) 是 β-三叶超家族的成员,具有特征性的三级结构三重对称性。然而,这种对称性的证据在初级序列水平上并不明显。这表明,虽然选择压力可能存在以保留(或收敛)对称的三级结构,但其他选择压力导致了进化过程中一级序列的分歧。通过对该蛋白家族 19 个成员的链内和同源序列比较,我们设计了 FGF-1 突变体,将核心堆积残基的子集限制在一级序列水平上三重对称。
结合 X 射线晶体学和差示扫描量热法评估了这些突变对结构和稳定性的影响。突变对结构和稳定性的影响可以通过使用 1.0A 探针半径检测到的核心内“微腔”的表征来合理化。结果表明,一级序列内的对称约束与填充良好的核心和接近野生型的稳定性兼容。然而,尽管整体热稳定性总体保持不变,但随着一级序列对称性的增加,非二态变性显着增加。因此,折叠特性而不是稳定性可能有助于对称蛋白质结构内不对称一级核心序列的选择压力。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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MICHAEL BLABER的其他文献
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{{ truncateString('MICHAEL BLABER', 18)}}的其他基金
Interactions between CNS-specific human kallikreins and the PA system in inflamma
CNS 特异性人激肽释放酶与炎症中 PA 系统之间的相互作用
- 批准号:
7849121 - 财政年份:2007
- 资助金额:
$ 0.31万 - 项目类别:
Interactions between CNS-specific human kallikreins and the PA system in inflamma
CNS 特异性人激肽释放酶与炎症中 PA 系统之间的相互作用
- 批准号:
7193334 - 财政年份:2007
- 资助金额:
$ 0.31万 - 项目类别:
STRUCTURE, STABILITY AND REGULATION OF HUMAN ACIDIC FGF
人类酸性 FGF 的结构、稳定性和调控
- 批准号:
6017093 - 财政年份:1996
- 资助金额:
$ 0.31万 - 项目类别:
STRUCTURE, STABILITY AND REGULATION OF HUMAN ACIDIC FGF
人类酸性 FGF 的结构、稳定性和调控
- 批准号:
2713756 - 财政年份:1996
- 资助金额:
$ 0.31万 - 项目类别:
STRUCTURE, STABILITY AND REGULATION OF HUMAN ACIDIC FGF
人类酸性 FGF 的结构、稳定性和调控
- 批准号:
6181088 - 财政年份:1996
- 资助金额:
$ 0.31万 - 项目类别:
STRUCTURE, STABILITY AND REGULATION OF HUMAN ACIDIC FGF
人类酸性 FGF 的结构、稳定性和调控
- 批准号:
2430503 - 财政年份:1996
- 资助金额:
$ 0.31万 - 项目类别:
STRUCTURE, STABILITY AND REGULATION OF HUMAN ACIDIC FGF
人类酸性 FGF 的结构、稳定性和调控
- 批准号:
2193795 - 财政年份:1996
- 资助金额:
$ 0.31万 - 项目类别:
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