کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2051415 | 1074200 | 2005 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: High resolution crystal structures of human Rab4a in its active and inactive conformations High resolution crystal structures of human Rab4a in its active and inactive conformations](/preview/png/2051415.png)
The Ras-related human GTPase Rab4a is involved in the regulation of endocytosis through the sorting and recycling of early endosomes. Towards further insight, we have determined the three-dimensional crystal structure of human Rab4a in its GppNHp-bound state to 1.6 Å resolution and in its GDP-bound state to 1.8 Å resolution, respectively. Despite the similarity of the overall structure with other Rab proteins, Rab4a displays significant differences. The structures are discussed with respect to the recently determined structure of human Rab5a and its complex with the Rab5-binding domain of the bivalent effector Rabaptin-5. The Rab4 specific residue His39 modulates the nucleotide binding pocket giving rise to a reduced rate for nucleotide hydrolysis and exchange. In comparison to Rab5, Rab4a has a different GDP-bound conformation within switch 1 region and displays shifts in position and orientation of the hydrophobic triad. The observed differences at the S2–L3–S3 region represent a new example of structural plasticity among Rab proteins and may provide a structural basis to understand the differential binding of similar effector proteins.
Journal: FEBS Letters - Volume 579, Issue 13, 23 May 2005, Pages 2821–2829