scholarly journals Human XTP3-B Forms an Endoplasmic Reticulum Quality Control Scaffold with the HRD1-SEL1L Ubiquitin Ligase Complex and BiP

2008 ◽  
Vol 283 (30) ◽  
pp. 20914-20924 ◽  
Author(s):  
Nobuko Hosokawa ◽  
Ikuo Wada ◽  
Koji Nagasawa ◽  
Tatsuya Moriyama ◽  
Katsuya Okawa ◽  
...  
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Ubiquitin Ligase ◽  
Ubiquitin Ligase Complex ◽  
Endoplasmic Reticulum Quality Control

scholarly journals In Vivo Action of the HRD Ubiquitin Ligase Complex: Mechanisms of Endoplasmic Reticulum Quality Control and Sterol Regulation

2001 ◽  
Vol 21 (13) ◽  
pp. 4276-4291 ◽  
Author(s):  
Richard G. Gardner ◽  
Alexander G. Shearer ◽  
Randolph Y. Hampton
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Ubiquitin Ligase ◽  
Sequence Similarity ◽  
High Specificity ◽  
Specific Sequence ◽  
Ubiquitin Ligase Complex ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzyme

ABSTRACT Ubiquitination is used to target both normal proteins for specific regulated degradation and misfolded proteins for purposes of quality control destruction. Ubiquitin ligases, or E3 proteins, promote ubiquitination by effecting the specific transfer of ubiquitin from the correct ubiquitin-conjugating enzyme, or E2 protein, to the target substrate. Substrate specificity is usually determined by specific sequence determinants, or degrons, in the target substrate that are recognized by the ubiquitin ligase. In quality control, however, a potentially vast collection of proteins with characteristic hallmarks of misfolding or misassembly are targeted with high specificity despite the lack of any sequence similarity between substrates. In order to understand the mechanisms of quality control ubiquitination, we have focused our attention on the first characterized quality control ubiquitin ligase, the HRD complex, which is responsible for the endoplasmic reticulum (ER)-associated degradation (ERAD) of numerous ER-resident proteins. Using an in vivo cross-linking assay, we directly examined the association of the separate HRDcomplex components with various ERAD substrates. We have discovered that the HRD ubiquitin ligase complex associates with both ERAD substrates and stable proteins, but only mediates ubiquitin-conjugating enzyme association with ERAD substrates. Our studies with the sterol pathway-regulated ERAD substrate Hmg2p, an isozyme of the yeast cholesterol biosynthetic enzyme HMG-coenzyme A reductase (HMGR), indicated that the HRD complex discerns between a degradation-competent “misfolded” state and a stable, tightly folded state. Thus, it appears that the physiologically regulated, HRD-dependent degradation of HMGR is effected by a programmed structural transition from a stable protein to a quality control substrate.

scholarly journals Lunapark Is a Component of a Ubiquitin Ligase Complex Localized to the Endoplasmic Reticulum Three-way Junctions

2016 ◽  
Vol 291 (35) ◽  
pp. 18252-18262 ◽  
Author(s):  
Yupeng Zhao ◽  
Ting Zhang ◽  
Huanhuan Huo ◽  
Yihong Ye ◽  
Yanfen Liu
Keyword(s):  
Endoplasmic Reticulum ◽  
Ubiquitin Ligase ◽  
Ubiquitin Ligase Complex

scholarly journals Mechanism of Class 1 (Glycosylhydrolase Family 47) α-Mannosidases Involved inN-Glycan Processing and Endoplasmic Reticulum Quality Control

2005 ◽  
Vol 280 (16) ◽  
pp. 16197-16207 ◽  
Author(s):  
Khanita Karaveg ◽  
Aloysius Siriwardena ◽  
Wolfram Tempel ◽  
Zhi-Jie Liu ◽  
John Glushka ◽  
...  
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Bond Cleavage ◽  
Substrate Analog ◽  
Acid And Base ◽  
Class 1 ◽  
Glycoside Bond ◽  
Endoplasmic Reticulum Quality Control ◽  
Mutant Forms ◽  
Hydrolytic Mechanism

Quality control in the endoplasmic reticulum (ER) determines the fate of newly synthesized glycoproteins toward either correct folding or disposal by ER-associated degradation. Initiation of the disposal process involves selective trimming ofN-glycans attached to misfolded glycoproteins by ER α-mannosidase I and subsequent recognition by the ER degradation-enhancing α-mannosidase-like protein family of lectins, both members of glycosylhydrolase family 47. The unusual inverting hydrolytic mechanism catalyzed by members of this family is investigated here by a combination of kinetic and binding analyses of wild type and mutant forms of human ER α-mannosidase I as well as by structural analysis of a co-complex with an uncleaved thiodisaccharide substrate analog. These data reveal the roles of potential catalytic acid and base residues and the identification of a novel3S1sugar conformation for the bound substrate analog. The co-crystal structure described here, in combination with the1C4conformation of a previously identified co-complex with the glycone mimic, 1-deoxymannojirimycin, indicates that glycoside bond cleavage proceeds through a least motion conformational twist of a properly predisposed substrate in the –1 subsite. A novel3H4conformation is proposed as the exploded transition state.

scholarly journals Crystal structure of a class I α1,2-mannosidase involved in N-glycan processing and endoplasmic reticulum quality control

2000 ◽  
Vol 19 (4) ◽  
pp. 581-588 ◽  
Author(s):  
François Vallée ◽  
Francesco Lipari ◽  
Patrick Yip ◽  
Barry Sleno ◽  
Annette Herscovics ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Class I ◽  
Endoplasmic Reticulum Quality Control

scholarly journals Overlapping function of Hrd1 and Ste24 in translocon quality control provides robust channel surveillance

2020 ◽  
Vol 295 (47) ◽  
pp. 16113-16120
Author(s):  
Avery M. Runnebohm ◽  
Kyle A. Richards ◽  
Courtney Broshar Irelan ◽  
Samantha M. Turk ◽  
Halie E. Vitali ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Ubiquitin Ligase ◽  
Biological Membranes ◽  
The Other ◽  
Growth Defect ◽  
Zinc Metalloprotease

Translocation of proteins across biological membranes is essential for life. Proteins that clog the endoplasmic reticulum (ER) translocon prevent the movement of other proteins into the ER. Eukaryotes have multiple translocon quality control (TQC) mechanisms to detect and destroy proteins that persistently engage the translocon. TQC mechanisms have been defined using a limited panel of substrates that aberrantly occupy the channel. The extent of substrate overlap among TQC pathways is unknown. In this study, we found that two TQC enzymes, the ER-associated degradation ubiquitin ligase Hrd1 and zinc metalloprotease Ste24, promote degradation of characterized translocon-associated substrates of the other enzyme in Saccharomyces cerevisiae. Although both enzymes contribute to substrate turnover, our results suggest a prominent role for Hrd1 in TQC. Yeast lacking both Hrd1 and Ste24 exhibit a profound growth defect, consistent with overlapping function. Remarkably, two mutations that mildly perturb post-translational translocation and reduce the extent of aberrant translocon engagement by a model substrate diminish cellular dependence on TQC enzymes. Our data reveal previously unappreciated mechanistic complexity in TQC substrate detection and suggest that a robust translocon surveillance infrastructure maintains functional and efficient translocation machinery.

scholarly journals Sorting things out through endoplasmic reticulum quality control

2010 ◽  
Vol 27 (8) ◽  
pp. 412-427 ◽  
Author(s):  
Taku Tamura ◽  
Johan C. Sunryd ◽  
Daniel N. Hebert
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Quality Control
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