Crystal structure of the DH/PH fragment of Dbs without bound GTPase.
Crystal structure of the DH/PH fragment of Dbs without bound GTPase.
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未结合 GTPase 的 Dbs DH/PH 片段的晶体结构。
DOI：
10.1016/j.str.2004.03.021
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Sondek,John
中科院分区：
文献类型：
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作者：
Worthylake,DavidK;Rossman,KentL;Sondek,John
DBL蛋白是Rho GTP酶的鸟嘌呤核苷酸交换因子，含有相邻的DBL同源(DH)和Pleckstrin同源(PH)结构域。这种域架构实际上是不变的，通常是完全交换潜力所必需的。与GTP酶结合的几种结构的DH/PH片段涉及核苷酸交换中的PH结构域。为了更全面地了解DH和PH结构域之间的功能联系，我们测定了没有结合GTP酶的DBS的DH/PH片段的晶体结构。这种结构一般类似于先前确定的与GTP酶结合的DBS结构，尽管在DH和PH结构域之间具有更明显的迁移性。这些比较表明，DBS的DH和PH结构域在空间上为结合GTP酶做好了准备，而可能由微妙的生物反应引起的域内构象的微小变化，如磷脂酰肌醇水平的变化，足以通过促进PH结构域和GTP酶之间的相互作用来加强交换。
Dbl proteins are guanine nucleotide exchange factors for Rho GTPases, containing adjacent Dbl homology (DH) and pleckstrin homology (PH) domains. This domain architecture is virtually invariant and typically required for full exchange potential. Several structures of DH/PH fragments bound to GTPases implicate the PH domain in nucleotide exchange. To more fully understand the functional linkage between DH and PH domains, we have determined the crystal structure of the DH/PH fragment of Dbs without bound GTPase. This structure is generally similar to previously determined structures of Dbs bound to GTPases albeit with greater apparent mobility between the DH and PH domains. These comparisons suggest that the DH and PH domains of Dbs are spatially primed for binding GTPases and small alterations in intradomain conformations that may be elicited by subtle biological responses, such as altered phosphoinositide levels, are sufficient to enhance exchange by facilitating interactions between the PH domain and GTPases.