Identification of a novel ubiquitin binding site of STAM1 VHS domain by NMR spectroscopy

Hong, Yoon Hun; Ahn, Hee Chul; Lim, Jong Gwan; Kim, Hong Man; Ji, Hye Young; Lee, Seung-a; Kim, Ji Hun; Park, Eun Young; Song, Hyun Kyu; Lee, Bong Jin

doi:10.1016/j.febslet.2008.12.034

Cited by 24 publications

(30 citation statements)

References 37 publications

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“…VHS domains are eight-helix bundles that contain an ubiquitin binding site formed by hydrophobic residues on helices 2 and 4 (Hong et al , 2009). These residues, in particular a Leu and a Trp from helix 2, are conserved in the VHS domains of ESCRT-0 subunits from yeast to mammals.…”

Section: Escrt Interactions and Functional Domainsmentioning

confidence: 99%

The ESCRT complexes

Hurley

2010

Critical Reviews in Biochemistry and Molecular Biology

304

296

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The ESCRT machinery consists of the peripheral membrane protein complexes, ESCRT-0, -I, -II, -III, and Vps4-Vta1, and the ALIX homodimer. The ESCRT system is required for degradation of unneeded or dangerous plasma membrane proteins; biogenesis of the lysosome and the yeast vacuole; the budding of most membrane enveloped viruses; the membrane abscission step in cytokinesis; macroautophagy; and several other processes. From their initial discovery in 2001-2002, the literature on ESCRTs has grown exponentially. This review will describe the structure and function of the six complexes noted above and summarizes current knowledge of their mechanistic roles in cellular pathways and in disease.

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Section: Escrt Interactions and Functional Domainsmentioning

confidence: 99%

The ESCRT complexes

Hurley

2010

Critical Reviews in Biochemistry and Molecular Biology

304

296

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“…STAM that inhibit their ability to associate with ubiquitin have been defined (11,13,21). To determine whether these point mutations affect the conformation of ESCRT-0, we introduced them both individually and simultaneously into the ESCRT-0 polycistronic expression construct.…”

Section: Point Mutations In the Ubds Of Hrs And Stam Do Not Affect Esmentioning

confidence: 99%

ESCRT-0 Assembles as a Heterotetrameric Complex on Membranes and Binds Multiple Ubiquitinylated Cargoes Simultaneously

Mayers¹,

Fyfe

Schuh³

et al. 2011

Journal of Biological Chemistry

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The ESCRT machinery consists of multiple protein complexes that collectively participate in the biogenesis of multivesicular endosomes (MVEs). The ESCRT-0 complex is composed of two subunits, Hrs and STAM, both of which can engage ubiquitinylated substrates destined for lysosomal degradation. Here, we conduct a comprehensive analysis of ESCRT-0:ubiquitin interactions using isothermal titration calorimetry and define the affinity of each ubiquitin-binding domain (UBD) within the intact ESCRT-0 complex. Our data demonstrate that ubiquitin binding is non-cooperative between the ESCRT-0 UBDs. Additionally, our findings show that the affinity of the Hrs double ubiquitin interacting motif (DUIM) for ubiquitin is more than 2-fold greater than that of UBDs found in STAM, suggesting that Hrs functions as the major ubiquitin-binding protein in ESCRT-0. In vivo, Hrs and STAM localize to endosomal membranes. To study recombinant ESCRT-0 assembly on lipid bilayers, we used atomic force microscopy. Our data show that ESCRT-0 forms mostly heterodimers and heterotetramers of Hrs and STAM when analyzed in the presence of membranes. Consistent with these findings, hydrodynamic analysis of endogenous ESCRT-0 indicates that it exists largely as a heterotetrameric complex of its two subunits. Based on these data, we present a revised model for ESCRT-0 function in cargo recruitment and concentration at the endosome.

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“…Some UBDs are relatively simple and autonomous, such as UIM/MIUs (Ub-interaction motifs), defined by small α helices that interact with the L8, I44, V70 hydrophobic patch on Ub (Hofmann and Falquet, 2001; Swanson et al, 2003). Other UBDs appear to be co-opted from different structural modules, some of which have well-defined functions and interactions distinct from Ub binding, including SH3 domains (Src homology 3), PH domains (pleckstrin homology), and VHS domains (Vps27, Hrs, STAM) (Hong et al, 2009; Ren and Hurley, 2010; Schreiner et al, 2008; Slagsvold et al, 2005; Stamenova et al, 2007). …”

Section: Introductionmentioning

confidence: 99%

WD40 Repeat Propellers Define a Ubiquitin-Binding Domain that Regulates Turnover of F Box Proteins

et al. 2010

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SUMMARY WD40-repeat β-propellers are found in a wide range of proteins involved in distinct biological activities. We define a large subset of WD40 β-propellers as a class of ubiquitin-binding domains. Using the β-propeller from Doa1/Ufd3 as a paradigm, we find the conserved top surface of the Doa1 β-propeller binds the hydrophobic patch of ubiquitin centered on residues I44, L8, and V70. Mutations that disrupt ubiquitin binding abrogate Doa1 function, demonstrating the importance of this interaction. We further demonstrate that WD40 β-propellers from a functionally diverse set of proteins bind ubiquitin in a similar fashion. This set includes members of the F box family of SCF ubiquitin E3 ligase adaptors. Using mutants defective in binding, we find that ubiquitin interaction by the F box protein Cdc4 promotes its autoubiquitination and turnover. Collectively, our results reveal a molecular mechanism that may account for how ubiquitin controls a broad spectrum of cellular activities.

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Identification of a novel ubiquitin binding site of STAM1 VHS domain by NMR spectroscopy

Cited by 24 publications

References 37 publications

The ESCRT complexes

The ESCRT complexes

ESCRT-0 Assembles as a Heterotetrameric Complex on Membranes and Binds Multiple Ubiquitinylated Cargoes Simultaneously

WD40 Repeat Propellers Define a Ubiquitin-Binding Domain that Regulates Turnover of F Box Proteins

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