Biology subjects

Osman, R.

Publications and source records attributed to Osman, R..

2 recordsLinked to original sources

bioRxiv2023

Structural basis of the interaction between ESV1 and LESV from Arabidopsis thaliana with starch glucans.

Starch is the major energy storage compound in plants. Whether it is transient or stored, it is accumulated in the form of insoluble, semi-crystalline granules. The structure of these granules is related to the structure of the main component: amylopectin. Amylopectin consists of linear polymers of glucose units linked by -1,4 bonds, forming double helices that combine to form the semi-crystalline lamellae of the granules, and -1,6 branching points that form the amorphous lamellae. This particular structure of amylopectin is linked to the action of isoamylases, which cut the excess of branching points and allow the granules to be structured. For a long time, it was thought that the action of these enzymes was responsible for the structuring of starch granules. Recently, two new proteins, LESV and ESV1, have been characterized and are involved in the phase transition of amylopectin (LESV) or in the maintenance of the granule structure (ESV1). These proteins share a tryptophan-rich domain folded into an antiparallel {beta}-sheet that is particularly well suited to bind amylopectin double helices. In this paper we present the structural study of these interactions using integrative structural biology approaches and show that LESV, in contrast to ESV1 can intervenes during amylopectin biosynthesis.

biophysics↗

bioRxiv2022

Substrate Binding and Inhibition of the Anion Exchanger 1 Transporter

Anion Exchanger 1 (AE1, SLC4A1) is the primary bicarbonate (HCO3-) transporter expressed in erythrocyte membranes where it mediates transport of CO2 between lungs and other tissues via import/export of bicarbonate. It is also a key regulator of erythrocyte structure and antigenic recognition. Previous biochemical studies, and a low-resolution crystal structure of the transmembrane domain have provided initial insight into AE1 structure and function. However, key questions remain regarding substrate binding and transport as well as the mechanism of inhibition. The orientation of the intracellular domain as well as the localization of lipid and sterol binding sites also remain enigmatic. We herein present seven novel high resolution cryo-EM structures of the full length human transporter in the apo, bicarbonate-bound, and several inhibitor-bound states combined with uptake- and computational studies. To our knowledge, these studies represent the first full length human, and substrate bound, SLC4 transporter structure. Our results reveal important molecular details about substrate binding and transport, as well as the diverse mechanisms of AE1 inhibition by both research chemicals and prescription drugs. We also provide novel insights into the full-length transporter architecture, identify the conformational space of the Diego blood antigen system and elucidate multiple lipid and sterol binding sites.

biochemistry↗