2BME

high resolution structure of GppNHp-bound human Rab4a

Summary for 2BME

• Entry DOI: 10.2210/pdb2bme/pdb
• Related: 2BMD
• Descriptor: RAS-RELATED PROTEIN RAB4A, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (6 entities in total)
• Functional Keywords: gtp-binding protein, vesicular transport, endocytosis, prenylation, protein transport, transport
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 4
• Total formula weight: 86793.94

Authors

Scheidig, A.J.,Huber, S.K. (deposition date: 2005-03-13, release date: 2005-04-25, Last modification date: 2023-12-13)

Primary citation

Huber, S.K.,Scheidig, A.J.
High Resolution Crystal Structures of Human Rab4A in its Active and Inactive Conformations.
FEBS Lett., 579:2821-, 2005

PubMed Abstract: 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 Angstroms resolution and in its GDP-bound state to 1.8 Angstroms 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.

PubMed: 15907487
DOI: 10.1016/J.FEBSLET.2005.04.020

Experimental method

X-RAY DIFFRACTION (1.57 Å)