5lpn
Structure of human Rab10 in complex with the bMERB domain of Mical-1Structure of human Rab10 in complex with the bMERB domain of Mical-1
Structural highlights
FunctionRAB10_HUMAN The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). That Rab is mainly involved in the biosynthetic transport of proteins from the Golgi to the plasma membrane. Regulates, for instance, SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane. In parallel, it regulates the transport of TLR4, a toll-like receptor to the plasma membrane and therefore may be important for innate immune response. Plays also a specific role in asymmetric protein transport to the plasma membrane within the polarized neuron and epithelial cells. In neurons, it is involved in axonogenesis through regulation of vesicular membrane trafficking toward the axonal plasma membrane while in epithelial cells, it regulates transport from the Golgi to the basolateral membrane. Moreover, may play a role in the basolateral recycling pathway and in phagosome maturation. According to PubMed:23263280, may play a role in endoplasmic reticulum dynamics and morphology controlling tubulation along microtubules and tubules fusion.[1] [2] [3] Publication Abstract from PubMedIn their active GTP-bound form, Rab proteins interact with proteins termed effector molecules. In this study we have thoroughly characterised a Rab effector domain that is present in proteins of the Mical and EHBP families, both known to act in endosomal trafficking. Within our study, we show that these effectors display a preference for Rab8 family proteins (Rab8, 10, 13 and 15) and that some of the effector domains can bind two Rab proteins via separate binding sites. Structural analysis allowed us to explain the specificity towards Rab8 family members and the presence of two similar Rab binding sites that must have evolved via gene duplication. This study is the first to thoroughly characterise a Rab effector protein that contains two separate Rab binding sites within a single domain, allowing Micals and EHBPs to bind two Rabs simultaneously, thus suggesting previously unknown functions of these effector molecules in endosomal trafficking. bMERB domains are bivalent Rab8 family effectors evolved by gene duplication.,Rai A, Oprisko A, Campos J, Fu Y, Friese T, Itzen A, Goody RS, Gazdag EM, Muller MP Elife. 2016 Aug 23;5. pii: e18675. doi: 10.7554/eLife.18675. PMID:27552051[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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