Bozorg, B. | Search bioRxiv

bioRxiv2019

Cholesterol binding to the sterol-sensing region of Niemann Pick C1 protein confines dynamics of its N-terminal domain

Lysosomal accumulation of cholesterol is a hallmark of Niemann Pick type C (NPC) disease caused by mutations primarily in the lysosomal membrane protein NPC1. NPC1 contains a transmembrane sterol sensing domain (SSD), which is supposed to regulate protein activity upon cholesterol binding, but the mechanisms underlying this process are poorly understood. Using atomistic simulations, we show that the binding of cholesterol to the SSD of NPC1 suppresses conformational dynamics of the luminal domains which otherwise bring the luminal N-terminal domain (NTD) closer to the lipid bilayer. The presence of an additional 20% membrane cholesterol has negligible impact on this process. We propose that cholesterol acts as an allosteric effector, and the modulation of NTD dynamics by the SSD-bound cholesterol constitutes an allosteric feedback mechanism in NPC1 which controls cholesterol abundance in the lysosomal membrane.

biophysics↗

bioRxiv2018

Anisotropic growth is achieved through the additive mechanical effect of material anisotropy and elastic asymmetry

Fast directional growth is a necessity for the young seedling: after germination, the seedling needs to quickly reach through the soil to begin its autotrophic life. In most dicot plants, this rapid escape is due to the anisotropic elongation of the hypocotyl, the columnar organ between the root and the shoot meristems. Such anisotropic growth is common in many plant organs and is canonically attributed to cell wall anisotropy produced by oriented cellulose fibers in the cell wall. More recently, a mechanism based on asymmetric cell wall elasticity has been proposed, produced by differential pectin biochemistry. Here we present a harmonizing model for anisotropic growth control in the dark-grown Arabidopsis hypocotyl: basic anisotropic information is provided by cellulose orientation (proxied by microtubules) and additive anisotropic information is provided by pectin-based elastic asymmetry in the epidermis. We demonstrate that hypocotyl growth was always anisotropic with axial and transverse walls growing differently, from germination. We present experimental evidence for pectin biochemical differences and wall mechanics underlying this differential growth. We demonstrate that pectin biochemical changes control the transition to rapid growth characteristic of Arabidopsis hypocotyl elongation, and provide evidence for a substantial mechanical role for pectin in the cell wall when microtubules are compromised. Lastly, our in silico modelling experiments indicate an additive combination for pectin biochemistry and cellulose orientation in promoting anisotropic growth.

plant biology↗