Domain insertions in protein structures.

Domain insertions in protein structures.
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DOI:
10.1016/j.jmb.2004.03.039
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发表时间:
2004-05-07
影响因子:
5.6
通讯作者:
Sasidharan, R
Sasidharan, R
中科院分区:
生物学2区
文献类型:
--
作者:
Aroul-Selvam, R;Hubbard, T;Sasidharan, R

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结构域是蛋白质的结构、功能或进化单位。蛋白质可包含单个结构域或结构域的组合。在多结构域蛋白质中,结构域几乎总是端到端出现,即一个结构域跟随另一个结构域的 C 末端。然而,这种常见模式也有例外,其中多结构域蛋白质是通过将一个结构域(插入)插入另一个结构域(亲本)而形成的。在这里,我们提供了蛋白质数据库(PDB)中已知插入的定量描述。我们发现在非冗余 PDB 中观察到的域组合中有 9% 是插入。尽管 90% 的插入仅涉及一个插入,但蛋白质显然可以具有多个(嵌套、两个结构域和三个结构域)插入。我们还观察到结构域的结构和功能之间的相关性及其作为亲本或插入片段的趋势。插入位置偏向亲本的 C 末端。我们观察到,与父上下文或单域上下文中的 N 到 C 距离相比,插入的 N 和 C 末端之间的原子距离明显更小。发现插入总是发生在父域的循环区域中。我们对结构域插入与蛋白质结构、功能和进化之间关系的观察对蛋白质工程具有重要意义。
Domains are the structural, functional or evolutionary units of proteins. Proteins can comprise a single domain or a combination of domains. In multi-domain proteins, the domains almost always occur end-to-end, i.e., one domain follows the C-terminal end of another domain. However, there are exceptions to this common pattern, where multi-domain proteins are formed by insertion of one domain (insert) into another domain (parent). Here, we provide a quantitative description of known insertions in the Protein Data Bank (PDB). We found that 9% of domain combinations observed in non-redundant PDB are insertions. Although 90% of all insertions involve only one insert, proteins can clearly have multiple (nested, two-domain and three-domain) inserts. We also observed correlations between the structure and function of a domain and its tendency to be found as a parent or an insert. There is a bias in insert position towards the C terminus of parents. We observed that the atomic distance between the N and C terminus of an insert is significantly smaller when compared to the N-to-C distance in a parent context or a single domain context. Insertions are found always to occur in loop regions of parent domains. Our observations regarding the relationship between domain insertions and the structure, function and evolution of proteins have implications for protein engineering.
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