Tetraspanin proteins play an important role in many cellular processes as they are key organizers of different receptors on the plasma membrane. Most tetraspanins are highly glycosylated at their large extracellular loop, however, little is known about the function of tetraspanin glycosylation in immune cells. In this study we investigated the effects of glycosylation of CD37 and CD53, two tetraspanins important for cellular and humoral immunity. Broad and cell-specific repertoires of N-glycosylated CD37 and CD53 were observed in human B cells ..read more

Highly homologous ubiquitin-binding shuttle proteins UBQLN1, UBQLN2 and UBQLN4 differ in both their specific protein quality control functions and their propensities to localize to stress-induced condensates, cellular aggregates and aggresomes. We previously showed that UBQLN2 phase separates , and that the phase separation propensities of UBQLN2 deletion constructs correlate with their ability to form condensates in cells. Here, we demonstrated that full-length UBQLN1, UBQLN2 and UBQLN4 exhibit distinct phase behaviors ..read more

Highly homologous ubiquitin-binding shuttle proteins UBQLN1, UBQLN2 and UBQLN4 differ in both their specific protein quality control functions and their propensities to localize to stress-induced condensates, cellular aggregates and aggresomes. We previously showed that UBQLN2 phase separates , and that the phase separation propensities of UBQLN2 deletion constructs correlate with their ability to form condensates in cells. Here, we demonstrated that full-length UBQLN1, UBQLN2 and UBQLN4 exhibit distinct phase behaviors ..read more

) is the most abundant divalent cation in the cell and is critical for numerous cellular processes. Despite its importance, the mechanisms of intracellular Mg transport and its regulation are poorly understood. MgtE is the main Mg transport system in almost half of bacterial species, and is an ortholog of mammalian SLC41A1 transporters, which are implicated in neurodegenerative diseases and cancer. Till date, only MgtE from ) has been extensively characterized mostly in detergent micelles, and gating-related structural dynamics in biologically-relevant membranes are scarce ..read more

-linked channelopathy is a neurological disorder characterized by seizures, motor abnormalities, and neurodevelopmental disabilities. The disease mechanisms are predicted to result from alterations in channel activity; however, only a subset of the patient-associated variants have been functionally studied. The localization of these variants within the tertiary structure or evaluation by pathogenicity algorithms has not been systematically assessed. In this study, 82 nonsynonymous patient-associated variants were mapped within the BK channel protein ..read more

We would like to thank all the reviewers who have donated their time and expertise to review papers submitted to . The list includes reviewers who served between November 1, 2022, and October 31, 2023 ..read more

Imaging Fluorescence Correlation Spectroscopy (Imaging FCS) is a powerful tool to extract information on molecular mobilities, actions and interactions in live cells, tissues and organisms. Nevertheless, several limitations restrict its applicability. First, FCS is data hungry, requiring 50,000 frames at 1 ms time resolution to obtain accurate parameter estimates. Second, the data size makes evaluation slow. Thirdly, as FCS evaluation is model-dependent, data evaluation is significantly slowed unless analytic models are available ..read more

Intrinsically disordered proteins are characterized by a conformational ensemble. While computational approaches such as molecular dynamics simulations have been used to generate such ensembles, their computational costs can be prohibitive. An alternative approach is to learn from data and train machine learning models to generate conformational ensembles of disordered proteins. This has been a relatively unexplored approach, and in this work we demonstrate a proof-of-principle approach to do so ..read more

Vascular endothelial cells (ECs) form a semi-permeable barrier separating vascular contents from the interstitium, thereby regulating the movement of water and molecular solutes across small intercellular gaps which are continuously forming and closing. Under inflammatory conditions, however, larger EC gaps form resulting in increased vascular leakiness to circulating fluid, proteins, and cells, resulting in organ edema and dysfunction responsible for key pathophysiologic findings in numerous inflammatory disorders ..read more

Rho-specific guanine dissociation inhibitors (RhoGDIs) play a crucial role in the regulation of Rho family GTPases. They act as negative regulators that prevent the activation of Rho GTPases by forming complexes with the inactive GDP-bound state of GTPase. Release of Rho GTPase from the RhoGDI-bound complex is necessary for Rho GTPase activation. Biochemical studies provide evidence of a "phosphorylation code", where phosphorylation of some specific residues of RhoGDI selectively releases its GTPase partner (RhoA, Rac1, Cdc42 etc ..read more