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  • Journal article

  • Cytoplasmic short linear motifs in ACE2 and integrin b3 link SARS-CoV-2 host cell receptors to endocytosis and autophagy

    • Authors : Kliche, Johanna; Ali, Muhammad; Ivarsson, Ylva (2020)

  • The spike protein of the SARS-CoV-2 interacts with angiotensin converting enzyme 2 (ACE2) and enters the host cell by receptor-mediated endocytosis. Concomitantly, evidence is pointing to the involvement of additional host cell receptors, such as integrins. The cytoplasmic tails of ACE2 and integrin β3 contain a plethora of predicted binding motifs. Here, we confirm the functionality of some of these motifs through affinity measurements. The class I PDZ&...
  • Journal article

  • The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context

    • Authors : M.M., Kutuzov; E.A., Belousova; T.A., Kurgina (2020)

  • Include base excision repair (BER) is implemented by a cellular signal PARylation catalysed by PARP1 and PARP2. Despite intensive studies, it is far from clear how BER is regulated by PARPs and how the roles are distributed between the PARPs. Here, we investigated the effects of PARP1, PARP2 and PARylation on activities of the main BER enzymes (APE1, Pol and LigIII) in combination with XRCC1 in the nucleosomal context. We constructed...
  • Journal article

  • Deflating the RNA Mg2+ bubble. Stereochemistry to the rescue!

    • Authors : Auffinger, Pascal; Ennifar, Eric; D’Ascenzo, Luigi (2020)

  • Evaluate the PDBid 6QNR and 6SJ6 models of the ribosome ionic structure and establish that stereochemical principles should always be considered when evaluating ion binding features, even when K+ anomalous signals are available as it is the case for 6QNR. Assignment errors can result in misleading conceptions of the solvent structure of ribosomes and other RNA systems and should therefore be avoided. Our analysis resulted in a significant decrease&#...
  • Journal article

  • ISRIB blunts the integrated stress response by allosterically antagonising the inhibitory effect of phosphorylated eIF2 on eIF2B

    • Authors : Zyryanova, Alisa F.; Kashiwagi, Kazuhiro; Rato, Claudia (2020)

  • ISRIB-mediated acceleration of eIF2B activity in vitro is observed preferentially in the presence of eIF2(αP) and is attenuated by mutations that desensitise eIF2B to the inhibitory effects of eIF2(αP). ISRIB’s efficacy as an ISR inhibitor in cells also depends on presence of eIF2(αP). Cryo-EM showed that engagement of both eIF2B regulatory sites by two eIF2(αP) molecules remodels both the ISRIB-binding pocket and the pockets that would engage eIF2α ...
  • Periodicals (Báo – Tạp chí)

  • Structure of the Human Signal Peptidase Complex Reveals the Determinants for Signal Peptide Cleavage

    • Authors : Liaci, A. Manuel (2020)

  • The signal peptidase complex (SPC) is an essential membrane complex in the endoplasmic reticulum (ER), here it removes signal peptides (SPs) from a large variety of secretory pre-proteins with exquisite specificity. Although the determinants of this process have been established empirically, the molecular details of SP recognition and removal remain elusive. Here, we show that the human SPC exists in two functional paralogs with distinct roteolytic subu...
  • Periodicals (Báo – Tạp chí)

  • Mammal ian Cel l Prol iferation Requires Noncatalytic Functions of O-GlcNAc Transferase

    • Authors : Levine, Zebulon G. (2020)

  • Developed approaches to replace endogenous OGT with separation-of-function variants to investigate the importance of OGT’s enzymatic activities for cell viability. Using genetic complementation, we found that OGT’s glycosyltransferase function is required for cell growth but its protease function is dispensable. We next used complementation to construct a cell line with degron-tagged wild-type OGT. When OGT was degraded to very low levels, cells stopped proliferating b...
  • Ebooks (Sách điện tử)

  • Disentangling the contribution of each descriptive characteristic of every single mutation to its functional effects

    • Authors : Sruthi, C. K.; Prakash, Meher K. (2020)

  • To address the former aspect using a framework of interpretable AI. Relations between the physico-chemical descriptors and their contributions to the mutational effects are extracted by analyzing the data on 29,832 variants from 8 systematic deep-mutational scan studies. It is found that the intuitive dependences of fitness and solubility on the distance of the amino acid from active site could be extracted and quantified. The dependence of the muta...