Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase

Lall, Patrick; Horgan, Conor P.; Oda, Shun-ichiro; Franklin, Edward; Sultana, Azmiri; Hanscom, Sara R.; McCaffrey, Mary W.; Khan, Amir R.

doi:10.1016/j.bbapap.2013.09.005

Cited by 14 publications

(11 citation statements)

References 76 publications

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“…In cell types lacking CLIC3, Rab25 may sort the integrin to lysosomes for degradation and thus inhibit cell invasion behaving like a tumor suppressor, while in cell types with high levels of CLIC3, Rab25 may recycle the integrin to promote cell migration and invasion [125]. In this regard, Rab25 is unique in its GTP-binding motif sequence DTAGLE as opposed to DTAGQE in other Rabs [126], which suggests inhibition of GTP hydrolysis and constitutive activation of Rab25 as a possible mechanism of aggressive metastasis seen in cancers with Rab25 overexpression, similar to the Q61L oncogenic mutation in Ras GTPases.…”

Section: Cancermentioning

confidence: 99%

Consequences of Rab GTPase dysfunction in genetic or acquired human diseases

Banworth

2017

Small GTPases

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Rab GTPases are important regulators of intracellular membrane trafficking in eukaryotes. Both activating and inactivating mutations in Rab genes have been identified and implicated in human diseases ranging from neurological disorders to cancer. In addition, altered Rab expression is often associated with disease prognosis. As such, the study of diseases associated with Rabs or Rab-interacting proteins has shed light on the important role of intracellular membrane trafficking in disease etiology. In this review, we cover recent advances in the field with an emphasis on cellular mechanisms.

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Section: Cancermentioning

confidence: 99%

Consequences of Rab GTPase dysfunction in genetic or acquired human diseases

Banworth

2017

Small GTPases

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“…However, this defect was observed only at early stages of cell growth and after extended culturing cells formed a normally polarized 2D monolayer with PCX being present at the apical domain. 7 Casanova and colleagues have reported that Rab25, a close homolog of Rab11 (sometimes called Rab11C) that can also interact with Rab11-FIP2 and myosin Vb, 25,26 was involved in apical recycling similarly to Rab11A, and that overexpression of Rab25 inhibited the apical delivery of polymeric immunoglobulin receptor. 27 In our observations, however, Rab25 depletion by specific siRNA treatment did not cause any defect in apical recycling or localization of PCX.…”

Section: Podocalyxin Trafficking In 2d Culture Systemmentioning

confidence: 99%

Regulation of podocalyxin trafficking by Rab small GTPases in epithelial cells

Mrozowska

Fukuda

2016

Small GTPases

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The characteristic feature of polarity establishment in MDCK II cells is transcytosis of apical glycoprotein podocalyxin (PCX) from the outer plasma membrane to the newly formed apical domain. This transcytotic event consists of multiple steps, including internalization from the plasma membrane, transport through early endosomes and Rab11-positive recycling endosomes, and delivery to the apical membrane. These steps are known to be tightly coordinated by Rab small GTPases, which act as molecular switches cycling between active GTP-bound and inactive GDPbound states. However, our knowledge regarding which sets of Rabs regulate particular steps of PCX trafficking was rather limited. Recently, we have performed a comprehensive analysis of Rab GTPase engagement in the transcytotic pathway of PCX during polarity establishment in 2-dimensional (2D) and 3-dimensional (3D) MDCK II cell cultures. In this Commentary we summarize our findings and set them in the context of previous reports.

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“…time. Despite the known structures of FIP2 in complex with Rab11 and Rab25 Lall et al, 2013), molecular replacement (MR) failed to provide a solution. Models of FIP2 from PDB entries 2gzd, 2gzh, 4c4p and 3tso research communications Arginine-stacking interactions stabilize a tetrameric FIP2 assembly.…”

Section: Resultsmentioning

confidence: 99%

“…Following 5 of Rab11, a hypervariable region of 43 residues is prenylated at two cysteine residues near the C-terminus of the 216-residue protein. This flexible region was dispensed with to enable crystallization of the complex (Lall et al, 2013). (b) Superposition of chain A of FIP2 with one of the -helices from the Rab11-FIP2 complex.…”

Section: Resultsmentioning

confidence: 99%

Crystal structure of the Rab-binding domain of Rab11 family-interacting protein 2

Kearney

Khan

2020

Acta Cryst Sect F

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The small GTPases Rab11, Rab14 and Rab25 regulate membrane trafficking through the recruitment of Rab11 family-interacting proteins (FIPs) to endocytic compartments. FIPs are multi-domain effector proteins that have a highly conserved Rab-binding domain (RBD) at their C-termini. Several structures of complexes of Rab11 with RBDs have previously been determined, including those of Rab11–FIP2 and Rab11–FIP3. In addition, the structures of the Rab14–FIP1 and Rab25–FIP2 complexes have been determined. All of the RBD structures contain a central parallel coiled coil in the RBD that binds to the switch 1 and switch 2 regions of the Rab. Here, the crystal structure of the uncomplexed RBD of FIP2 is presented at 2.3 Å resolution. The structure reveals antiparallel α-helices that associate through polar interactions. These include a remarkable stack of arginine residues within a four-helix bundle in the crystal lattice.

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Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase

Cited by 14 publications

References 76 publications

Consequences of Rab GTPase dysfunction in genetic or acquired human diseases

Consequences of Rab GTPase dysfunction in genetic or acquired human diseases

Regulation of podocalyxin trafficking by Rab small GTPases in epithelial cells

Crystal structure of the Rab-binding domain of Rab11 family-interacting protein 2

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