The structure of the C-terminal actin-binding domain of talin

Talin is a large dimeric protein that couples integrins to cytoskeletal actin. Here, we report the structure of the C-terminal actin-binding domain of talin, the core of which is a five-helix bundle linked to a C-terminal helix responsible for dimerisation. The NMR structure of the bundle reveals a conserved surface-exposed hydrophobic patch surrounded by positively charged groups. We have mapped the actin-binding site to this surface and shown that helix 1 on the opposite side of the bundle negatively regulates actin binding. The crystal structure of the dimerisation helix reveals an antiparallel coiled-coil with conserved residues clustered on the solvent-exposed face. Mutagenesis shows that dimerisation is essential for filamentous actin (F-actin) binding and indicates that the dimerisation helix itself contributes to binding. We have used these structures together with small angle X-ray scattering to derive a model of the entire domain. Electron microscopy provides direct evidence for binding of the dimer to F-actin and indicates that it binds to three monomers along the long-pitch helix of the actin filament

A rapid rate of sex-chromosome turnover and non-random transitions in true frogs.

The canonical model of sex-chromosome evolution predicts that, as recombination is suppressed along sex chromosomes, gametologs will progressively differentiate, eventually becoming heteromorphic. However, there are numerous examples of homomorphic sex chromosomes across the tree of life. This homomorphy has been suggested to result from frequent sex-chromosome turnovers, yet we know little about which forces drive them. Here, we describe an extremely fast rate of turnover among 28 species of Ranidae. Transitions are not random, but converge on several chromosomes, potentially due to genes they harbour. Transitions also preserve the ancestral pattern of male heterogamety, in line with the hot-potato model of sex-chromosome transitions, suggesting a key role for mutation-load accumulation in non-recombining genomic regions. The importance of mutation-load selection in frogs might result from the extreme heterochiasmy they exhibit, making frog sex chromosomes differentiate immediately from emergence and across their entire length

A rapid rate of sex-chromosome turnover and non-random transitions in true frogs.

The canonical model of sex-chromosome evolution predicts that, as recombination is suppressed along sex chromosomes, gametologs will progressively differentiate, eventually becoming heteromorphic. However, there are numerous examples of homomorphic sex chromosomes across the tree of life. This homomorphy has been suggested to result from frequent sex-chromosome turnovers, yet we know little about which forces drive them. Here, we describe an extremely fast rate of turnover among 28 species of Ranidae. Transitions are not random, but converge on several chromosomes, potentially due to genes they harbour. Transitions also preserve the ancestral pattern of male heterogamety, in line with the 'hot-potato' model of sex-chromosome transitions, suggesting a key role for mutation-load accumulation in non-recombining genomic regions. The importance of mutation-load selection in frogs might result from the extreme heterochiasmy they exhibit, making frog sex chromosomes differentiate immediately from emergence and across their entire length

A rapid rate of sex-chromosome turnover and non-random transitions in true frogs

© The Author(s).The canonical model of sex-chromosome evolution predicts that, as recombination is suppressed along sex chromosomes, gametologs will progressively differentiate, eventually becoming heteromorphic. However, there are numerous examples of homomorphic sex chromosomes across the tree of life. This homomorphy has been suggested to result from frequent sex-chromosome turnovers, yet we know little about which forces drive them. Here, we describe an extremely fast rate of turnover among 28 species of Ranidae. Transitions are not random, but converge on several chromosomes, potentially due to genes they harbour. Transitions also preserve the ancestral pattern of male heterogamety, in line with the ‘hot-potato’ model of sex-chromosome transitions, suggesting a key role for mutation-load accumulation in non-recombining genomic regions. The importance of mutation-load selection in frogs might result from the extreme heterochiasmy they exhibit, making frog sex chromosomes differentiate immediately from emergence and across their entire length.This work was primarily funded by two grants (31003A_166323 & CRSII3_147625) awarded by the Swiss National Science Foundation to N.P.Peer Reviewe