RSS

PDB:2C7N

Protein Name

Rabex-5/ubiquitin complex

Species

Homo sapiens (human)

Biological Context

Ubiquitination of proteins regulates various cellular processes. Ubiquitination of proteins was discovered as a proteolytic signal at first, but non-proteolytic functions of ubiquitin such as DNA repair, transcriptional regulation, and endocytosis were also discovered later. The functions of ubiquitin largely depend on its protein interaction. Many proteins have ubiquitin binding domains (UBDs) which interact with ubiquitin. This interaction reconstitutes the signaling network, and changes the cellular signaling.

Structure Description

2c7n2c7n_x2c7n_y

The structure described here is Rabex-5-ubiquitin complex. Rabex-5 is a guanine nucleotide exchange factor for Rab-5, a small GTPase that regulates endocytosis signaling. Rabex-5 binds to ubiquitin through two independent UBDs. One is RUZ which contain a zinc finger motif. RUZ binds to a region centered on D58 of ubiquitin different from canonical I44 surface. The other is MIU, a newly identified UBD, that contains a sequence motif similar to that of a known UBD, UIM, but in the reverse direction. MIU binds to the canonical I44 surface of ubiquitin. These two UBDs may facilitate the hand-off of the ubiquitinated cargo in the protein transport processes. The significance of Rabex-5-ubiquitin interaction in the physiological condition has not been well-known, but it is proposed that the interaction with ubiquitinated EGFRs (epidermal growth factor receptors) allows relocalization of Rabex-5 to the plasma membrane or to early endosomes, thereby allowing activation of Rab5.

Protein Data Bank (PDB)

References

Source

Penengo, L. Mapelli, M. Murachelli, A.G. Confalonieri, S. Magri, L. Musacchio, A. Di Fiore, P.P. Polo, S. Schneider, T.R.; "Crystal Structure of the Ubiquitin Binding Domains of Rabex-5 Reveals Two Modes of Interaction with Ubiquitin."; Cell(Cambridge,Mass.); (2006) 124:1183-1095. PubMed:16499958

Others

UniProt:Q53FG0_HUMAN UniProt:UBIQ_BOVIN

author: Daisuke Ino


Japanese version:PDB:2C7N