Characterization of the flexible portions of fibrinogen
纤维蛋白原柔性部分的表征
基本信息
- 批准号:7082242
- 负责人:
- 金额:$ 18.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-07-05 至 2008-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Although recently reported three-dimensional structures of fibrinogen and its core fragments have been very revealing, key regions of these molecules are inherently flexible and have not yielded to the X-ray approach. These mobile regions, which amount to almost one-third of the molecule, are extremely important in a functional sense, and ignorance of their whereabouts is a distinct limitation to understanding fibrin clot formation. The mobile regions include the amino-terminal segments of the alpha and beta chains where the thrombin-sensitive bonds occur, the carboxyl-terminal segment of the alpha chain where factor XIII-catalyzed gamma-gamma dimer formation takes place, and, finally, the entire carboxyl-terminal section of the alpha chain, commonly called the alphaC domain. The latter plays a poorly understood role in the association of protofibrils and also involves factor XIII-induced cross-links. The goal of the current project is to establish the whereabouts of the flexible regions in native fibrinogen by using conventional but carefully crafted biochemistry experiments. The experiments fall into two general realms, both employing the same general procedures. In one set of experiments the biochemistry is conducted directly on crystals of native fibrinogen (chicken) where the bulk of the molecule is constrained and only the regions of interest are able to move about and interact. Thrombin and other specific enzymes will be used to specifically remove the fibrinopeptides directly in the crystal, after which selective chemical cross-linking will be used to join the newly exposed A and/or B knobs within each molecule. Similar experiments will be conducted on fibrin (human), where the constraints are somewhat different. These studies are aimed at finding how far apart the mobile knobs are from each other, on the average. Other experiments will be performed that immobilize the a chain carboxyl regions in situ, again both in crystals of native fibrinogen and in fibrin clots, by taking advantage of easily reduced disulfide bonds. The goal here is to find how the alphaC domains are situated relative to each other. In a related study, hybrid fibrins prepared from fibrinogens from different species will be used to follow polymerization events, especially the interactions and cross-linking of gamma-chain carboxyl terminal segments on the one hand and alphaC domains on the other. These studies are aimed at determining the degree of specificity involved in the assembly of fibrin units and protofibrils as well as the relative locations of the regions involved.
描述(申请人提供):尽管最近报道的纤维蛋白原及其核心片段的三维结构非常具有启发性,但这些分子的关键区域天生灵活,并未屈服于X射线方法。这些移动区域几乎占到分子的三分之一,在功能上非常重要,而对它们的下落的无知是理解纤维蛋白凝块形成的一个明显限制。可移动区域包括发生凝血酶敏感键的α和β链的氨基末端片段,因子XIII催化的伽马-伽马二聚体形成的阿尔法链的羧基末端片段,以及阿尔法链的整个羧基末端部分,通常称为αC结构域。后者在原纤维的关联中扮演的角色知之甚少,也涉及XIII因子诱导的交联链。目前项目的目标是通过使用常规但精心制作的生物化学实验来确定天然纤维蛋白原中柔性区域的位置。这些实验分为两个一般领域,都采用了相同的一般程序。在一组实验中,生物化学直接在天然纤维蛋白原(鸡)的晶体上进行,分子的大部分受到限制,只有感兴趣的区域能够四处移动和相互作用。凝血酶和其他特定的酶将被用来专门去除晶体中的纤维蛋白肽,之后将使用选择性化学交联来连接每个分子中新暴露的A和/或B旋钮。类似的实验将在纤维蛋白(人体)上进行,限制条件略有不同。这些研究旨在找出平均而言,移动旋钮之间的距离有多远。还将进行其他实验,利用容易还原的二硫键,在天然纤维蛋白原晶体和纤维蛋白凝块中原位固定a链羧基区域。这里的目标是找出字母C结构域是如何相对于彼此定位的。在一项相关的研究中,来自不同物种的纤维蛋白原制备的杂化纤维蛋白将被用于跟踪聚合事件,特别是伽马链羧基末端片段与αC结构域的相互作用和交联。这些研究的目的是确定纤维蛋白单位和原纤维组装所涉及的特异性程度以及所涉及区域的相对位置。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
RUSSELL F DOOLITTLE其他文献
RUSSELL F DOOLITTLE的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('RUSSELL F DOOLITTLE', 18)}}的其他基金
STRUCTURAL STUDIES ON HOW FIBRINOGEN IS TRANSFORMED INTO FIBRIN
纤维蛋白原如何转化为纤维蛋白的结构研究
- 批准号:
7370366 - 财政年份:2006
- 资助金额:
$ 18.86万 - 项目类别:
Characterization of the flexible portions of fibrinogen
纤维蛋白原柔性部分的表征
- 批准号:
7251961 - 财政年份:2005
- 资助金额:
$ 18.86万 - 项目类别:
Characterization of the flexible portions of fibrinogen
纤维蛋白原柔性部分的表征
- 批准号:
6962377 - 财政年份:2005
- 资助金额:
$ 18.86万 - 项目类别:
STRUCTURAL STUDIES OF CRUSTACEAN CLOTTING PROTEIN
甲壳动物凝血蛋白的结构研究
- 批准号:
7183085 - 财政年份:2005
- 资助金额:
$ 18.86万 - 项目类别:
CRYSTAL STRUCTURE OF HUMAN FIBRINOGEN FRAGMENT D
人纤维蛋白原片段 D 的晶体结构
- 批准号:
6658620 - 财政年份:2002
- 资助金额:
$ 18.86万 - 项目类别:
CRYSTAL STRUCTURE OF HUMAN FIBRINOGEN FRAGMENT D & COMPLEX
人纤维蛋白原片段 D 的晶体结构
- 批准号:
6586529 - 财政年份:2002
- 资助金额:
$ 18.86万 - 项目类别:
CRYSTAL STRUCTURE OF HUMAN FIBRINOGEN FRAGMENT D
人纤维蛋白原片段 D 的晶体结构
- 批准号:
6586653 - 财政年份:2002
- 资助金额:
$ 18.86万 - 项目类别:
CRYSTAL STRUCTURE OF HUMAN FIBRINOGEN FRAGMENT D & COMPLEX
人纤维蛋白原片段 D 的晶体结构
- 批准号:
6658496 - 财政年份:2002
- 资助金额:
$ 18.86万 - 项目类别:
CRYSTAL STRUCTURE OF HUMAN FIBRINOGEN FRAGMENT D & COMPLEX
人纤维蛋白原片段 D 的晶体结构
- 批准号:
6437447 - 财政年份:2001
- 资助金额:
$ 18.86万 - 项目类别:
CRYSTAL STRUCTURE OF HUMAN FIBRINOGEN FRAGMENT D
人纤维蛋白原片段 D 的晶体结构
- 批准号:
6437571 - 财政年份:2001
- 资助金额:
$ 18.86万 - 项目类别: