You, H. | bioRxiv Science

bioRxiv2018

The holdase function of Escherichia coli Hsp70 (DnaK) chaperone

In Escherichia coli, the DnaK/DnaJ/GrpE system plays a critical role in mediating protein refolding and buffering against protein aggregation due to environmental stress. The underlying mechanism remains unclear. In this work, we probe the activity of DnaK/DnaJ/GrpE system with single-molecule protein refolding assay using tandem repeats of titin immunoglobulin 27 (I27)8. We provide direct evidence that DnaK in apo- and ADP-bound state is predominantly a holdase, which kinetically stabilizes the polyprotein in its unfolded form. Binding of ATP relieves DnaKs holding, allowing protein refolding. The presence of co-chaperone DnaJ and GrpE modulates this holding-release switching, possibly by altering DnaKs nucleotide state. Our findings thus provide important insights to the molecular mechanism of DnaK/DnaJ/GrpE system.

molecular biology↗

bioRxiv2016

Long-range suppressive influences from the visual surround can be explained by anatomically plausible recruitment of local competition in a model of columnar cortex

Although neurons in columns of visual cortex of adult carnivores and primates share similar orientation tuning preferences, responses of nearby neurons are surprisingly sparse and temporally uncorrelated, especially in response to complex visual scenes. The mechanisms underlying this counter-intuitive combination of response properties are still unknown. Here we present a computational model of columnar visual cortex which explains experimentally observed integration of complex features across the visual field, and which is consistent with anatomical and physiological profiles of cortical excitation and inhibition. In this model, sparse local excitatory connections within columns, coupled with strong unspecific local inhibition and functionally-specific long-range excitatory connections across columns, give rise to competitive dynamics that reproduce experimental observations. Our results explain surround modulation of responses to simple and complex visual stimuli, including reduced correlation of nearby excitatory neurons, increased excitatory response selectivity, increased inhibitory selectivity, and complex orientation-tuning of surround modulation.

neuroscience↗