Selma Maric

Karolinska Institutet | KI · Department of Medical Biochemistry and Biophysics

Phosphatidylcholine (PC) is a major component of eukaryotic cell membranes and one of the most commonly used phospholipids for reconstitution of membrane proteins into carrier systems such as lipid vesicles, micelles and nanodiscs. Selectively deuterated versions of this lipid have many applications, especially in structural studies using technique...

Structural studies of membrane proteins remain a great experimental challenge. Functional reconstitution into artificial nanoscale bilayer disc carriers that mimic the native bilayer environment allows the handling of membrane proteins in solution. This enables the use of small-angle scattering techniques for fast and reliable structural analysis....

Lipid-protein interactions can function as “co-factors” that affect the properties / function of transmembrane proteins. Herein, the interaction between anionic dimyristoylphosphatidylglycerol (DMPG) and zwitterionic dimyristoylphosphatidylcholine (DMPC) with the amphiphatic membrane scaffold protein (MSP), were studied. Two 25 kDa MSP wrap around...

Nanodiscs are self-assembled 10 nm particles composed of lipid bilayer patches, stabilized by helical amphipathic belt proteins. The size, monodispersity and well-defined structure make the nanodiscs a popular model for the biological cell membrane, especially for structural and functional studies of membrane proteins. The structures and properties...

The M17 leucine aminopeptidase of the intraerythrocytic stages of the malaria parasite Plasmodium falciparum (PfLAP) plays a role in releasing amino acids from host hemoglobin that are used for parasite protein synthesis, growth, and development. This enzyme represents a target at which new antimalarials could be designed since metalloaminopeptidas...

Apolipoprotein E (ApoE), an important mediator of lipid transportation in plasma and the nervous system, plays a large role in diseases such as atherosclerosis and Alzheimer's. The major allele variants ApoE3 and ApoE4 differ only by one amino acid. However, this difference has major consequences for the physiological behaviour of each variant. In...

Lipoproteins play a central role in the development of atherosclerosis. High and low-density lipoproteins (HDL and LDL), known as ‘good’ and ‘bad’ cholesterol, respectively, remove and/or deposit lipids into the artery wall. Hence, insight into lipid exchange processes between lipoproteins and cell membranes is of particular importance in understan...

Atherosclerosis is the main killer in the western world. Today’s clinical markers include the total level of cholesterol and high-/low-density lipoproteins, which often fails to accurately predict the disease. The relationship between the lipid exchange capacity and lipoprotein structure should explain the extent by which they release or accept lip...

The deuteration of biomolecules provides advanced opportunities for neutron scattering studies. For low resolution studies using techniques such as small-angle neutron scattering and neutron reflection, the level of deuteration of a sample can be varied to match the scattering length density of a specific D2O/H2O solvent mixture. This can be of maj...

Plasma-membrane Ca²⁺-ATPases expel Ca²⁺ from the cytoplasm and are key regulators of Ca²⁺ homeostasis in eukaryotes. They are autoinhibited under low Ca²⁺ concentrations. Calmodulin (CaM)-binding to a unique regulatory domain releases the autoinhibition and activates the pump. However, the structural basis for this activation, including the overall...

Structural studies of integral membrane proteins (IMPs) are challenging, as many of them are inactive or insoluble in the absence of a lipid environment. Here, we describe an approach making use of fractionally deuterium labeled "stealth carrier" nanodiscs that are effectively invisible to low-resolution neutron diffraction and enable structural st...

Lipoproteins play a key role in the onset and development of atherosclerosis, the formation of lipid plaques at blood vessel walls. The plaque formation, as well as subsequent calcification, involves not only endothelial cells but also connective tissue, and is closely related to a wide range of cardiovascular syndromes, that together constitute th...

Deuteration of biomolecules has a great impact on both quality and scope of neutron scattering experiments. Cholesterol is a major component of mammalian cells, where it plays a critical role in membrane permeability, rigidity and dynamics, and contributes to specific membrane structures such as lipid rafts. Cholesterol is the main cargo in low and...

Cholesterol is an essential component of mammalian membranes that is known to induce a series of physicochemical changes in the lipid bilayer. Such changes include the formation of liquid ordered phases with an increased thickness and configurational order as compared to liquid disordered phases. For saturated lipid membranes, cholesterol molecules...

High and low density lipoproteins (HDL and LDL) are thought to play vital roles in the onset and development of atherosclerosis; the biggest killer in the western world. Key issues of initial lipoprotein (LP) interactions at cellular membranes need to be addressed including LP deposition and lipid exchange. Here we present a protocol for monitoring...

Atherosclerosis and its clinical consequences are the leading cause of death in the west. While many studies throughout the last decades have aimed at understanding the disease, the clinical markers in use today still fail to accurately predict the risks. The role of the main clinical indicator of today, the low density lipoprotein (LDL), in deposi...

Cysteine is an important amino acid in the redox defense of Mycobacterium tuberculosis, primarily as a building block of mycothiol. Genetic studies have implicated de novo cysteine biosynthesis in pathogen survival in infected macrophages, in particular for persistent M. tuberculosis. Here, we report on the identification and characterization of po...

Here, we bind the sodium dependent amino acid transporter on nitrilotriacetic acid/polyethylene glycol functionalized gold sensors in detergent and perform a detergent-lipid exchange with phosphatidylcholine. We characterize the LeuT structure in the adsorbed film by magnetic contrast neutron reflection using the predicted model from molecular dyna...