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As proteins travel through the endoplasmic reticulum (ER), a quality-control system retains newly synthesized polypeptides and supports their maturation. Only properly folded proteins are released to their designated destinations. Proteins that cannot mature are left to accumulate, impairing the function of the ER. To maintain homeostasis, the protein-quality-control system singles out aberrant polypeptides and delivers them to the cytosol, where they are destroyed by the proteasome. The importance of this pathway is evident from the growing list of pathologies associated with quality-control defects in the ER.

Effector proteins of innate immune systems recognize specific non-self epitopes. Tectonins are a family of β-propeller lectins conserved from bacteria to mammals that have been shown to bind bacterial lipopolysaccharide (LPS). We present experimental evidence that two Tectonins of fungal and animal origin have a specificity for O-methylated glycans. We show that Tectonin 2 of the mushroom Laccaria bicolor (Lb-Tec2) agglutinates Gram-negative bacteria and exerts toxicity toward the model nematode Caenorhabditis elegans , suggesting a role in fungal defense against bacteria and nematodes. Biochemical and genetic analysis of these interactions revealed that both bacterial agglutination and nematotoxicity of Lb-Tec2 depend on the recognition of methylated glycans, namely O-methylated mannose and fucose residues, as part of bacterial LPS and nematode cell-surface glycans. In addition, a C. elegans gene, termed samt-1 , coding for a candidate membrane transport protein for the presumptive donor substrate of glycan methylation, S-adenosyl-methionine, from the cytoplasm to the Golgi was identified. Intriguingly, limulus lectin L6, a structurally related antibacterial protein of the Japanese horseshoe crab Tachypleus tridentatus , showed properties identical to the mushroom lectin. These results suggest that O-methylated glycans constitute a conserved target of the fungal and animal innate immune system. The broad phylogenetic distribution of O-methylated glycans increases the spectrum of potential antagonists recognized by Tectonins, rendering this conserved protein family a universal defense armor.

Misfolded proteins of the endoplasmic reticulum (ER) are targeted to the cytoplasm for proteasomal degradation. Key components of this process are ER membrane‐bound ubiquitin ligases. These ligases associate with the cytoplasmic AAA‐ATPase Cdc48p/p97, which is thought to support the release of malfolded proteins from the ER. Here, we characterize a yeast protein complex containing the ubiquitin ligase Hrd1p and the ER membrane proteins Hrd3p and Der1p. Hrd3p binds malfolded proteins in the ER lumen enabling their delivery to downstream components. Therefore, we propose that Hrd3p acts as a substrate recruitment factor for the Hrd1p ligase complex. Hrd3p function is also required for the association of Cdc48p with Hrd1p. Moreover, our data demonstrate that recruitment of Cdc48p depends on substrate processing by the Hrd1p ligase complex. Thus, the Hrd1p ligase complex unites substrate selection in the ER lumen and polyubiquitination in the cytoplasm and links these processes to the release of ER proteins via the Cdc48p complex.

In Saccharomyces cerevisiae , the synthesis of chitin is temporally and spatially regulated through the transport of Chs3p (chitin synthase III) to the plasma membrane in the bud neck region. Traffic of Chs3p from the trans ‐Golgi network (TGN)/early endosome to the plasma membrane requires the function of Chs5p and Chs6p. Chs6p belongs to a family of four proteins that we have named ChAPs for Ch s5p‐ A rf1p‐binding P rotein s . Here, we show that all ChAPs physically interact not only with Chs5p but also with the small GTPase Arf1p. A short sequence at the C‐terminus of the ChAPs is required for protein function and the ability to bind to Chs5p. Simultaneous disruption of two members, Δ bud7 and Δ bch1 , phenocopies a Δ chs6 or Δ chs5 deletion with respect to Chs3p transport. Moreover, the ChAPs interact with each other and can form complexes. In addition, they are all at least partially localized to the TGN in a Chs5p‐dependent manner. Most importantly, several ChAPs can interact physically with Chs3p. We propose that the ChAPs facilitate export of cargo out of the Golgi.

A quality-control system surveys the lumen of the endoplasmic reticulum for terminally misfolded proteins. Polypeptides singled out by this system are ultimately degraded by the cytosolic ubiquitin-proteasome pathway. Key components of both the endoplasmic reticulum quality-control system and the degradation machinery have been identified, but a connection between the two systems has remained elusive. Here, we report an association between the endoplasmic reticulum quality-control lectin Yos9p and Hrd3p, a component of the ubiquitin-proteasome system that links these pathways. We identify designated regions in the luminal domain of Hrd3p that interact with Yos9p and the ubiquitin ligase Hrd1p. Binding of misfolded proteins occurs through Hrd3p, suggesting that Hrd3p recognises proteins that deviate from their native conformation, whereas Yos9p ensures that only terminally misfolded polypeptides are degraded.

For defined contribution plans, a member's interest upon death must be distributed within specified time frames depending on the type of beneficiary, as follows: * Within five years to a non-individual beneficiary; * Within 10 years to an individual designated beneficiary; and * Within 10 years to an eligible designated beneficiary unless the eligible designated beneficiary elects distributions over the beneficiary's life expectancy; provided that if the eligible designated beneficiary is a minor child, the interest must be fully distributed by age 31. Public Safety Health Insurance Premium Deductions The Final Regulations clarify that a distribution under Code Section 402(1) (distributions with respect to eligible retired public safety officers to pay health insurance premiums) will count towards the individuals RMD for the applicable year. Annuity Contract Purchased Under a Defined Contribution Plan The Final Regulations confirm that payments under an annuity contract purchased under a defined contribution plan cannot extend past the otherwise applicable full distribution deadline (i.e., for a designated beneficiary, the ten-year rule). The Proposed Regulations would establish that a distribution from a designated Roth account in a year in which the employee is required to take an RMD does not count toward the RMD requirement. [...]the Roth distribution would be eligible to be rolled over to a Roth IRA if it otherwise meets the requirements for an eligible rollover distribution.

ELIMINATION OF FIVE-YEAR REMEDIAL AMENDMENT CYCLE SYSTEM Effective January 1, 2017, the IRS eliminated the staggered, five-year remedial amendment cycle system for individually designed plans; most governmental plans are individually designed plans. [...]as of that date, the IRS will no longer accept applications for determination letters based on the five-year remedial amendment cycle system. [...]consistent with Announcement 2016-32, Treasury and the IRS recently issued an update to the Employee Plans Compliance Resolution System (EPCRS) revenue procedure with Rev. Proc. 2016-51 (issued on September 29, 2016).12 Under Rev. Proc. 2016-51, the IRS modified and superseded EPCRS and also incorporated changes that were announced with Rev. Proc. 2015-2713 (which provided certain updates regarding, in part, the correction of overpayments), and Rev. Proc. 2015-27 (which addressed the correction of failures with respect to automatic contribution failures and encouraging the early correction of employee elective deferrals).