Ras-related protein Rab-11B is a
protein that in humans is encoded by the RAB11Bgene.[5][6] Rab11b is reported as most abundantly
expressed in brain, heart and testes.
Rab (Ras-related in brain) proteins form the largest section of the
Ras superfamily of small
GTPases. The Rab family proteins regulate intracellular membrane trafficking processes including
vesicle budding, tethering, and fusion. The isoforms
Rab11a, Rab11b, and Rab11c/
Rab25 constitute the Rab11 subfamily based on specific
sequence motifs.[7] While RAB11A is located on
chromosome 15[8] and RAB11C on
chromosome 1, RAB11B is placed on
chromosome 19. Rab11 proteins are implicated in
endocytosis and
exocytosis.[9] Rab11b is reported as most abundantly expressed in brain, heart and testes.[10] Early studies with deletions of RAB11 homologs in Saccharomyces cerevisiae proved their importance in cell survival.[11][12]
Despite sharing high
sequence homology, Rab11a and Rab11b appear to reside within distinct vesicle compartments.[13] Majority of Rab11b neither colocalize with
transferrin receptor nor with the
polymeric IgA receptor. This protein also exhibits a dependence on the microtubule
cytoskeleton that is different from Rab11a.[13] High sequence diversity in the C-terminal hypervariable region is responsible for variable membrane targeting between these proteins.
Function
Members of the Rab11 subfamily act in recycling of proteins from the
endosomes to the
plasma membrane, in transport of molecules from the
trans-Golgi network to the plasma membrane and in
phagocytosis. This subfamily also acts in polarized transport in
epithelial cells.[14][15][16][17][18] Whereas most studies refer to the Rab11a isoform, little is known about Rab11b so far. Rab11b localizes predominantly in the pericentriolar recycling compartment and serves as an important component of the vesicular machinery.[19] It is required for the transfer of internalized
transferrin from the recycling compartment to the plasma membrane for which active Rab11b as well as
GTP hydrolysis is necessary.[19]
Structure
All Ras GTPases consist of a similar core structure and highly conserved
P-loop, switch 1 and switch 2 regions. The Rab11b monomer exhibits a typical Ras-like, small GTPase fold with a six stranded
β-sheet core (β1-β6) surrounded by five major
α-helices (α1-α5)[16] and one minor α-helix (α6). According to the sequence similarity to other Rab GTPases can be assumed that they show closely resembling characteristics in nucleotide binding and
hydrolysis. However, Rab11 isoforms could differ in hydrolysis kinetics owing to the differences in
conformation, since Rab11a and Rab11b do not show an α-helical switch 2 region like other Rab GTPases. Rab11b shares 90% amino acid identity to Rab11a.[16] Kinetic experiments with Rab11a/b and Rab11-interacting proteins (FIPs) indicate that FIPs cannot differentiate between GTP-bound Rab11a and Rab11b in vitro.[20] The major divergence reveals in the inactive state. While Pasqualato et al. crystallized inactive Rab11a as a dimer in the asymmetric unit, Scapin et al. observed single crystallographically independent monomers of both the GDP- and the GppNHp-bound Rab11b structures.[16][21]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Zhu AX, Zhao Y, Flier JS (Dec 1994). "Molecular cloning of two small GTP-binding proteins from human skeletal muscle". Biochemical and Biophysical Research Communications. 205 (3): 1875–82.
doi:
10.1006/bbrc.1994.2889.
PMID7811277.
^Lai F, Stubbs L, Artzt K (Aug 1994). "Molecular analysis of mouse Rab11b: a new type of mammalian YPT/Rab protein". Genomics. 22 (3): 610–6.
doi:
10.1006/geno.1994.1434.
PMID8001972.
^
abLapierre LA, Dorn MC, Zimmerman CF, Navarre J, Burnette JO, Goldenring JR (Nov 2003). "Rab11b resides in a vesicular compartment distinct from Rab11a in parietal cells and other epithelial cells". Experimental Cell Research. 290 (2): 322–31.
doi:
10.1016/s0014-4827(03)00340-9.
PMID14567990.
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4.
doi:
10.1016/0378-1119(94)90802-8.
PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56.
doi:
10.1016/S0378-1119(97)00411-3.
PMID9373149.
Schlierf B, Fey GH, Hauber J, Hocke GM, Rosorius O (Aug 2000). "Rab11b is essential for recycling of transferrin to the plasma membrane". Experimental Cell Research. 259 (1): 257–65.
doi:
10.1006/excr.2000.4947.
PMID10942597.
Scapin SM, Carneiro FR, Alves AC, Medrano FJ, Guimarães BG, Zanchin NI (Jun 2006). "The crystal structure of the small GTPase Rab11b reveals critical differences relative to the Rab11a isoform". Journal of Structural Biology. 154 (3): 260–8.
doi:
10.1016/j.jsb.2006.01.007.
PMID16545962.