Structural basis for ubiquitin recognition by the human ESCRT-II EAP45 GLUE domain

Alam, Steven L.; Langelier, Charles; Whitby, Frank G.; Koirala, Sajjan; Robinson, Howard; Hill, Christopher P.; Sundquist, Wesley I.

doi:10.1038/nsmb1160

Cited by 69 publications

(60 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies suggested that ubiquitylation of certain membrane proteins is a very critical signal for its sorting into intraluminal vesicles (ILVs) of endosomes, then MVBs (Henne et al, 2011;Marchese et al, 2008;Raiborg and Stenmark, 2009). In addition, in yeast and mammalian cells, Vps36 can recognize the ubiquitylated proteins (Alam et al, 2006;Hirano et al, 2006;Teo et al, 2006). In the experiment, we found that Vps36 recognizes Smo in the absence of Hh, but not in yeast two-hybrid assay.…”

Section: The Ubiquitin Signal Mediates the Interaction Between Smo Anmentioning

confidence: 65%

“…The GLUE domain interacts with 3-phosphorylated phosphoinositides and one of the NZF domains is responsible for recognizing ubiquitin (Teo et al, 2006). However, the GLUE domain rather than the NZF domain, has been found in the mammalian and Drosophila homologs of Vps36 (Alam et al, 2006;Hirano et al, 2006;Irion and St Johnston, 2007;Slagsvold et al, 2005). To test whether the Drosophila Vps36 GLUE domain plays a role in Smo interaction with Vps36, we performed additional Co-IP experiments.…”

Section: Vps36 Interacts With Smo In the Absence Of Hh Signalmentioning

confidence: 99%

See 1 more Smart Citation

Drosophila Vps36 is involved in Hh signaling by regulating Smo trafficking

Yang

Mao

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

SummaryThe hedgehog (Hh) signaling pathway plays a very important role in metazoan development by controlling pattern formation. Malfunction of the Hh signaling pathway leads to numerous serious human diseases, including congenital disorders and cancers. The seven-transmembrane domain protein Smoothened (Smo) is a key transducer of the Hh signaling pathway, and mediates the graded Hh signal across the cell plasma membrane, thereby inducing the proper expression of downstream genes. Smo accumulation on the cell plasma membrane is regulated by its C-tail phosphorylation and the graded Hh signal. The inhibitory mechanism for Smo membrane accumulation in the absence of Hh, however, is still largely unknown. Here, we report that Vps36 of the ESCRT-II complex regulates Smo trafficking between the cytosol and plasma membrane by specifically recognizing the ubiquitin signal on Smo in the absence of Hh. Furthermore, in the absence of Hh, Smo is ubiquitylated on its cytoplasmic part, including its internal loops and C-tail. Taken together, our data suggest that the ESCRT-II complex, especially Vps36, has a special role in controlling Hh signaling by targeting the membrane protein Smo for its trafficking in the absence of Hh, thereby regulating Hh signaling activity.

show abstract

Section: The Ubiquitin Signal Mediates the Interaction Between Smo Anmentioning

confidence: 65%

Section: Vps36 Interacts With Smo In the Absence Of Hh Signalmentioning

confidence: 99%

Drosophila Vps36 is involved in Hh signaling by regulating Smo trafficking

Yang

Mao

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…The PHD fold of Pru domain from Rpn13 subunit of proteasome binds the common hydrophobic pocket of Ub through exclusive loops (35,36). However, the GLUE domain from ESCRT-II EAP45 binds the Ile 44 -containing surface of Ub through the residues within secondary structural elements including C-terminal helix (37), although it also adopts a PHD fold.…”

Section: Discussionmentioning

confidence: 99%

Structural Basis for Ubiquitin Recognition by a Novel Domain from Human Phospholipase A2-activating Protein

Zhou

Gao

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Ubiquitin (Ub) is an essential modifier conserved in all eukaryotes from yeast to human. Phospholipase A 2 -activating protein (PLAA), a mammalian homolog of yeast DOA1/UFD3, has been proposed to be able to bind with Ub, which plays important roles in endoplasmic reticulum-associated degradation, vesicle formation, and DNA damage response. We have identified a core domain from the PLAA family ubiquitin-binding region of human PLAA (residues 386 -465, namely PFUC) that can bind Ub and elucidated its solution structure and Ubbinding mode by NMR approaches. The PFUC domain possesses equal population of two conformers in solution by cis/ trans-isomerization, whereas the two isomers exhibit almost equivalent Ub binding abilities. This domain structure takes a novel fold consisting of four ␤-strands and two ␣-helices, and the Ub-binding site on PFUC locates in the surface of ␣2-helix, which is to some extent analogous to those of UBA, CUE, and UIM domains. This study provides structural basis and biochemical information for Ub recognition of the novel PFU domain from a PLAA family protein that may connect ubiquitination and degradation in endoplasmic reticulum-associated degradation.The eukaryotic secreted proteins are translocated into the endoplasmic reticulum after synthesis in cytosol. Misfolded or abnormally assembled proteins should be targeted for degradation through the endoplasmic reticulum-associated degradation (ERAD) 3 pathway (1, 2). This pathway involves many molecular steps: unfolded protein response in the endoplasmic reticulum lumen, retrotranslocation back into the cytosol, ubiquitin (Ub) conjugation, delivery of ubiquitinated proteins to proteasome, and degradation of the substrates by proteases (3, 4).A yeast protein DOA1/UFD3 has been shown to bind to CDC48 by both indirect and direct ways (5-7), suggesting that DOA1 may be involved in ERAD. Evidence indicates that DOA1 directly competes with UFD2 at the same docking site on CDC48, which determines whether a substrate is multiubiquitinated and routed to the proteasome for degradation or deubiquitinated and released for other purposes (8). The direct interaction between DOA1 and Ub was suggested by recent studies (7, 9). Moreover, DOA1 also plays roles in the monoubiquitination of histone H2B and proliferating cell nuclear antigen (10) and in sorting ubiquitinated membrane proteins into multivesicular bodies (11).The mammalian homolog of DOA1 is called phospholipase A 2 -activating protein (PLAA), which can bind to P97/VCP (a CDC48 homolog) with its C-terminal domain PUL (7). Having high sequence similarity (31% identity) with DOA1, PLAA is proposed to possess similar function of DOA1. Like DOA1, PLAA has an N-terminal WD40 domain with yet unknown function. The central region of PLAA contains a putative PLAA family ubiquitin-binding (PFU) domain, which is supposed to bind with Ub as observed in yeast DOA1 (7). Although the mechanism underlying the function of PLAA remains unclear, Ub binding of PLAA might be the central role that connects ubiquitin...

show abstract

“…Both Vps23 and Tsg101 bind Ub similarly, using a Ub E2 variant (UEV) domain ,Teo et al 2004b. Mammalian Vps36/EAP45 uses a GLUE domain to bind both phosphorylated phosphatidylinositols and Ub (Alam et al 2006,Hirano et al 2006,Teo et al 2006. Several residue differences in the yeast Vps36 GLUE domain are predicted to prevent its Ub binding.…”

Section: Lumen Ubiquitin As a Sorting Signalmentioning

confidence: 99%

Biogenesis and Function of Multivesicular Bodies

Piper

Katzmann

2007

Annu. Rev. Cell Dev. Biol.

679

660

View full text Add to dashboard Cite

The two major cellular sites for membrane protein degradation are the proteasome and the lysosome. Ubiquitin attachment is a sorting signal for both degradation routes. For lysosomal degradation, ubiquitination triggers the sorting of cargo proteins into the lumen of late endosomal multivesicular bodies (MVBs)/endosomes. MVB formation occurs when a portion of the limiting membrane of an endosome invaginates and buds into its own lumen. Intralumenal vesicles are degraded when MVBs fuse to lysosomes. The proper delivery of proteins to the MVB interior relies on specific ubiquitination of cargo, recognition and sorting of ubiquitinated cargo to endosomal subdomains, and the formation and scission of cargo-filled intralumenal vesicles. Over the past five years, a number of proteins that may directly participate in these aspects of MVB function and biogenesis have been identified. However, major questions remain as to exactly what these proteins do at the molecular level and how they may accomplish these tasks.

show abstract

Structural basis for ubiquitin recognition by the human ESCRT-II EAP45 GLUE domain

Cited by 69 publications

References 14 publications

Drosophila Vps36 is involved in Hh signaling by regulating Smo trafficking

Drosophila Vps36 is involved in Hh signaling by regulating Smo trafficking

Structural Basis for Ubiquitin Recognition by a Novel Domain from Human Phospholipase A2-activating Protein

Biogenesis and Function of Multivesicular Bodies

Contact Info

Product

Resources

About