Structural and Biochemical Basis of Yos9 Protein Dimerization and Possible Contribution to Self-association of 3-Hydroxy-3-methylglutaryl-Coenzyme A Reductase Degradation Ubiquitin-Ligase Complex

Hanna, Jennifer; Schütz, Anja; Zimmermann, Franziska; Behlke, Joachim; Sommer, Thomas; Heinemann, Udo

doi:10.1074/jbc.m111.317644

Cited by 13 publications

(24 citation statements)

References 52 publications

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“…OS-9 is composed of two domains: a mannose recognition homology (MRH) lectin domain located at the N-terminus and a C-terminal domain that in yeast serves a dimerization function 17; 18 (see Figure 1 for constructs used in these studies). To determine which OS-9 domain interacts with Grp94, we co-expressed His-tagged Grp94 with full length or truncated OS-9 constructs in E. coli and used affinity purification of the His-tagged Grp94 to test for OS-9 association.…”

Section: Resultsmentioning

confidence: 99%

“…14; 15; 16 OS-9-bound TMPs are delivered to the HRD1/SEL1 E3 ubiquitin ligase retrotranslocation complex by interaction of SEL1 with the N-terminal portion of OS-9. 14; 17; 18 Although it is unknown whether Grp94 interacts as a binary complex with OS-9, or in a ternary complex with OS-9 and TMP, evidence suggests that Grp94 dissociates from OS-9 prior to interaction of OS-9 with SEL1. 11 …”

Section: Introductionmentioning

confidence: 99%

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Characterization of the Grp94/OS-9 Chaperone–Lectin Complex

Seidler

Shinsky

Hong

et al. 2014

Journal of Molecular Biology

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Grp94 is a macromolecular chaperone belonging to the hsp90 family and is the most abundant glycoprotein in the endoplasmic reticulum of mammals. In addition to its essential role in protein folding, Grp94 was proposed to participate in the ER associated degradation (ERAD) quality control pathway by interacting with the lectin OS-9, a sensor for terminally misfolded proteins (TMPs). To understand how OS-9 interacts with ER chaperone proteins, we mapped its interaction with Grp94. Glycosylation of the full length Grp94 protein was essential for OS-9 binding, although deletion of the Grp94 N-terminal domain relieved this requirement suggesting that the effect was allosteric rather than direct. Although yeast OS-9 is composed of a well-established N-terminal MRH lectin domain and a C-terminal dimerization domain, we find that the C-terminal domain of OS-9 in higher eukaryotes contains ‘mammalian-specific insets’ that are specifically recognized by the middle and C-terminal domains of Grp94. Additionally, the Grp94 binding domain in OS-9 was found to be intrinsically disordered. The biochemical analysis of the interacting regions provides insight into the manner by which the two associate, and additionally hints at a plausible biological role for the Grp94/OS-9 complex.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of the Grp94/OS-9 Chaperone–Lectin Complex

Seidler

Shinsky

Hong

et al. 2014

Journal of Molecular Biology

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“…Very recently, crystal structure of C-terminal domain of Yos9 adjacent to the MRH domain has been reported ( Fig. 7) (66). This study provided structural insights into a dimeric state of the membrane-embedded ERAD machinery in the luminal side.…”

Section: F Perspectivementioning

confidence: 85%

Molecular and Structural Basis for Sugar Recognition by Mannose 6-Phosphate Receptor Homology Domain-Containing Lectins and Proteins

Satoh

2012

TIGG

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N -Linked glycans play important roles in the determination of glycoprotein fates in cells through interactions with a variety of intracellular lectins. Most of the intracellular lectins possess carbohydrate recognition domain, which is homologous to legume lectins or mannose 6-phosphate receptors (MPRs). These lectins are categorized as L-type or P-type lectins. Besides L-type lectins, recently accumulated frontal affinity chromatography and glycan microarray data have demonstrated that P-type lectins and the MPR homology (MRH) domain-containing proteins have distinct sugar-binding specificity profiles. Furthermore, newly emerged three-dimensional structural data have revealed sugar recognition mechanisms at an atomic level. This review summarizes the current state of knowledge of molecular and structural basis for sugar recognition by P-type lectins and MRH domain-containing proteins that control folding, transport, and degradation of N-linked glycoproteins in the secretory pathway.

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“…Unlike the yeast ortholog, Yos9p, mammalian OS-9 does not contain an ER retention signal. Yos9 is a dimer, and the ~170-residue dimerization domain, which is adjacent to the C terminus of the MRH domain, has been crystallized [76]. …”

Section: ) Other Mrh Domain-containing Proteins In the Secretory Patmentioning

confidence: 99%

Glucosidase II and MRH-Domain Containing Proteins in the Secretory Pathway

D’Alessio

Dahms²

2015

CPPS

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N -glycosylation in the endoplasmic reticulum (ER) consists of the transfer of a pre-assembled glycan conserved among species (Glc3Man9GlcNAc2) from a lipid donor to a consensus sequence within a nascent protein that is entering the ER. The protein-linked glycans are then processed by glycosidases and glycosyltransferases in the ER producing specific structures that serve as signalling molecules for the fate of the folding glycoprotein: to stay in the ER during the folding process, to be retrotranslocated to the cytosol for proteasomal degradation if irreversibly misfolded, or to pursue transit through the secretory pathway as a mature glycoprotein. In the ER, each glycan signalling structure is recognized by a specific lectin. A domain similar to that of the mannose 6-phosphate receptors (MPRs) has been identified in several proteins of the secretory pathway. These include the beta subunit of glucosidase II (GII), a key enzyme in the early processing of the transferred glycan that removes middle and innermost glucoses and is involved in quality control of glycoprotein folding in the ER (QC), the lectins OS-9 and XTP3-B, proteins involved in the delivery of ER misfolded proteins to degradation (ERAD), the gamma subunit of the Golgi GlcNAc-1-phosphotransferase, an enzyme involved in generating the mannose 6-phosphate (M6P) signal for sorting acidic hydrolases to lysosomes, and finally the MPRs that deliver those hydrolytic enzymes to the lysosome. Each of the MRH-containing proteins recognizes a different signalling N-glycan structure. Three-dimensional structures of some of the MRH domains have been solved, providing the basis to understand recognition mechanisms.

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Structural and Biochemical Basis of Yos9 Protein Dimerization and Possible Contribution to Self-association of 3-Hydroxy-3-methylglutaryl-Coenzyme A Reductase Degradation Ubiquitin-Ligase Complex

Cited by 13 publications

References 52 publications

Characterization of the Grp94/OS-9 Chaperone–Lectin Complex

Characterization of the Grp94/OS-9 Chaperone–Lectin Complex

Molecular and Structural Basis for Sugar Recognition by Mannose 6-Phosphate Receptor Homology Domain-Containing Lectins and Proteins

Glucosidase II and MRH-Domain Containing Proteins in the Secretory Pathway

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