TY - JOUR AB - Deposits of misfolded proteins in the human brain are associated with the development of many neurodegenerative diseases. Recent studies show that these proteins have common traits even at the monomer level. Among them, a polyglutamine region that is present in huntingtin is known to exhibit a correlation between the length of the chain and the severity as well as the earliness of the onset of Huntington disease. Here, we apply bias exchange molecular dynamics to generate structures of polyglutamine expansions of several lengths and characterize the resulting independent conformations. We compare the properties of these conformations to those of the standard proteins, as well as to other homopolymeric tracts. We find that, similar to the previously studied polyvaline chains, the set of possible transient folds is much broader than the set of known-to-date folds, although the conformations have different structures. We show that the mechanical stability is not related to any simple geometrical characteristics of the structures. We demonstrate that long polyglutamine expansions result in higher mechanical stability than the shorter ones. They also have a longer life span and are substantially more prone to form knotted structures. The knotted region has an average length of 35 residues, similar to the typical threshold for most polyglutamine-related diseases. Similarly, changes in shape and mechanical stability appear once the total length of the peptide exceeds this threshold of 35 glutamine residues. We suggest that knotted conformers may also harm the cellular machinery and thus lead to disease. AU - Gómez Sicilia, Àngel AU - Sikora, Mateusz K AU - Cieplak, Marek AU - Carrión Vázquez, Mariano ID - 1566 IS - 10 JF - PLoS Computational Biology TI - An exploration of the universe of polyglutamine structures VL - 11 ER - TY - GEN AU - Tugrul, Murat AU - Paixao, Tiago AU - Barton, Nicholas H AU - Tkačik, Gašper ID - 9712 TI - Other fitness models for comparison & for interacting TFBSs ER - TY - GEN AU - Gómez Sicilia, Àngel AU - Sikora, Mateusz K AU - Cieplak, Marek AU - Carrión Vázquez, Mariano ID - 9714 TI - An exploration of the universe of polyglutamine structures - submission to PLOS journals ER - TY - GEN AU - Trubenova, Barbora AU - Novak, Sebastian AU - Hager, Reinmar ID - 9715 TI - Mathematical inference of the results ER - TY - JOUR AB - The fitness effects of symbionts on their hosts can be context-dependent, with usually benign symbionts causing detrimental effects when their hosts are stressed, or typically parasitic symbionts providing protection towards their hosts (e.g. against pathogen infection). Here, we studied the novel association between the invasive garden ant Lasius neglectus and its fungal ectosymbiont Laboulbenia formicarum for potential costs and benefits. We tested ants with different Laboulbenia levels for their survival and immunity under resource limitation and exposure to the obligate killing entomopathogen Metarhizium brunneum. While survival of L. neglectus workers under starvation was significantly decreased with increasing Laboulbenia levels, host survival under Metarhizium exposure increased with higher levels of the ectosymbiont, suggesting a symbiont-mediated anti-pathogen protection, which seems to be driven mechanistically by both improved sanitary behaviours and an upregulated immune system. Ants with high Laboulbenia levels showed significantly longer self-grooming and elevated expression of immune genes relevant for wound repair and antifungal responses (β-1,3-glucan binding protein, Prophenoloxidase), compared with ants carrying low Laboulbenia levels. This suggests that the ectosymbiont Laboulbenia formicarum weakens its ant host by either direct resource exploitation or the costs of an upregulated behavioural and immunological response, which, however, provides a prophylactic protection upon later exposure to pathogens. AU - Konrad, Matthias AU - Grasse, Anna V AU - Tragust, Simon AU - Cremer, Sylvia ID - 1993 IS - 1799 JF - Proceedings of the Royal Society of London Series B Biological Sciences SN - 0962-8452 TI - Anti-pathogen protection versus survival costs mediated by an ectosymbiont in an ant host VL - 282 ER -