Kristina Djinovic - Academia.edu (original) (raw)

Papers by Kristina Djinovic

Journal of Molecular Biology, 1994

Journal of Inorganic Biochemistry, 1991

Science Advances, 2021

Sarcomeric proteins FATZ-1 and α-actinin-2 associate in a tight fuzzy complex, which forms phase-... more Sarcomeric proteins FATZ-1 and α-actinin-2 associate in a tight fuzzy complex, which forms phase-separated condensates.

Proceedings of the National Academy of Sciences, 2020

The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin–binding prote... more The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin–binding proteins, is fundamentally important in eukaryotes. α-Actinins are major F-actin bundlers that are inhibited by Ca2+in nonmuscle cells. Here we report the mechanism of Ca2+-mediated regulation ofEntamoeba histolyticaα-actinin-2 (EhActn2) with features expected for the common ancestor ofEntamoebaand higher eukaryotic α-actinins. Crystal structures of Ca2+-free and Ca2+-boundEhActn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of theEhActn2 CaMD for Ca2+, binding of which can only be regulated in the presence of physiological concentrations of Mg2+. Ca2+binding triggers an increase in protein multidomain rigidity, reducing conformational flexibility of F-actin–binding domains via interdomain cross-talk and consequently inhibiting F-actin bundling. In vivo studies uncover thatEhActn2 plays an important r...

Acta Crystallographica Section A Foundations and Advances, 2019

Crystals, 2019

The presence of isolated metal cations, far from any other atom, is not uncommon in protein cryst... more The presence of isolated metal cations, far from any other atom, is not uncommon in protein crystal structures. A systematic survey of the Protein Data Bank showed that nearly 8% of the metal cations are naked, more frequently if they can interact only electrostatically with their neighbors. Surprisingly, this seemed to be only weakly related to the crystallographic resolution.

ABSTRACTMORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic di... more ABSTRACTMORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic distribution, being found in both prokaryotes and eukaryotes. Despite this ubiquity, they remain poorly characterised at both a structural and a functional level compared to other common repeats. In functional terms, they are often assumed to be lipid-binding modules that mediate membrane targeting. We addressed this putative activity by focusing on a protein composed solely of MORN repeats –Trypanosoma bruceiMORN1. Surprisingly, no evidence for binding to membranes or lipid vesicles by TbMORN1 could be obtained either in vivo or in vitro. Conversely, TbMORN1 did interact with individual phospholipids. High- and low-resolution structures of the MORN1 protein fromTrypanosoma bruceiand homologous proteins from the parasitesToxoplasma gondiiandPlasmodium falciparumwere obtained using a combination of macromolecular crystallography, small-angle X-ray scattering, and electron microscopy. This e...

Molecular Biology Reports, 2019

Chronic overuse of common pharmaceuticals, e.g. acetaminophen (paracetamol), often leads to the d... more Chronic overuse of common pharmaceuticals, e.g. acetaminophen (paracetamol), often leads to the development of acute liver failure (ALF). This study aimed to elucidate the effect of cultured mesenchymal stem cells (MSCs) proteome on the onset of liver damage and regeneration dynamics in animals with ALF induced by acetaminophen, to test the liver protective efficacy of MSCs proteome depending on the oxygen tension in cell culture, and to blueprint protein components responsible for the effect. Protein compositions prepared from MSCs cultured in mild hypoxic (5% and 10% O 2) and normal (21% O 2) conditions were used to treat ALF induced in mice by injection of acetaminophen. To test the effect of reduced oxygen tension in cell culture on resulting MSCs proteome content we applied a combination of high performance liquid chromatography and mass-spectrometry (LC-MS/MS) for the identification of proteins in lysates of MSCs cultured at different O 2 levels. The treatment of acetaminophen-administered animals with proteins released from cultured MSCs resulted in the inhibition of inflammatory reactions in damaged liver; the area of hepatocyte necrosis being reduced in the first 24 h. Compositions obtained from MSCs cultured at lower O 2 level were shown to be more potent than a composition prepared from normoxic cells. A comparative characterization of protein pattern and identification of individual components done by a cytokine assay and proteomics analysis of protein compositions revealed that even moderate hypoxia produces discrete changes in the expression of various subsets of proteins responsible for intracellular respiration and cell signaling. The application of proteins prepared from MSCs grown in vitro at reduced oxygen tension significantly accelerates healing process in damaged liver tissue. The proteomics data obtained for different preparations offer new information about the potential candidates in the MSCs protein repertoire sensitive to oxygen tension in culture medium, which can be involved in the generalized mechanisms the cells use to respond to acute liver failure. Keywords Acute liver failure • Stem cells • Conditioned medium • Acetaminophen • Proteome • Hypoxia Abbreviations ALF Acute liver failure MSCs Mesenchymal stem cells NC-MSCs MSCs cultured in conditions of normoxia (21% oxygen) HC-MSCs MSCs cultured in conditions of hypoxia (10% or 5% oxygen) Electronic supplementary material The online version of this article (

Scientific Reports, 2017

Myotilin is a component of the sarcomere where it plays an important role in organisation and mai... more Myotilin is a component of the sarcomere where it plays an important role in organisation and maintenance of Z-disk integrity. This involves direct binding to F-actin and filamin C, a function mediated by its Ig domain pair. While the structures of these two individual domains are known, information about their relative orientation and flexibility remains limited. We set on to characterise the Ig domain pair of myotilin with emphasis on its molecular structure, dynamics and phylogeny. First, sequence conservation analysis of myotilin shed light on the molecular basis of myotilinopathies and revealed several motifs in Ig domains found also in I-band proteins. In particular, a highly conserved Glu344 mapping to Ig domain linker, was identified as a critical component of the inter-domain hinge mechanism. Next, SAXS and molecular dynamics revealed that Ig domain pair exists as a multi-conformation species with dynamic exchange between extended and compact orientations. Mutation of AKE m...

Acta Crystallographica Section A Foundations and Advances, 2016

Cellular and Molecular Life Sciences, 2017

Journal of Muscle Research and Cell Motility

Abstracts of the 41st European Muscle Conference; Structure-Function (Track 1)

Journal of the Chemical Society, Dalton Transactions, 1991

Metal Complexes of I .2=Diaminobenzene Derivatives. Determination of the Oxidation State of the L... more Metal Complexes of I .2=Diaminobenzene Derivatives. Determination of the Oxidation State of the Ligands through Crystallographic Data t ... Oliviero Carugo,*.e Kristina Djinovi6,6 Menico Rizzi and Carla Bisi Castellani a Dipartimento di Medicina Preventiva, Occupazionale e ...

Journal of the Chemical Society, Dalton Transactions, 1993

... Comparison of the co-ordinative behaviour of calcium(II) and magnesium(II) from crystallograp... more ... Comparison of the co-ordinative behaviour of calcium(II) and magnesium(II) from crystallographic data. Oliviero Carugo, Kristina Djinović and Menico Rizzi J. Chem. Soc., Dalton Trans., 1993, 2127-2135. DOI: 10.1039/DT9930002127 ...

Journal of the Chemical Society, Dalton Transactions, 1992

ABSTRACT

Life (Basel, Switzerland), Jan 21, 2015

Sm and Sm-like proteins represent an evolutionarily conserved family with key roles in RNA metabo... more Sm and Sm-like proteins represent an evolutionarily conserved family with key roles in RNA metabolism. Sm-based regulation is diverse and can range in scope from eukaryotic mRNA splicing to bacterial quorum sensing, with at least one step in these processes being mediated by an RNA-associated molecular assembly built on Sm proteins. Despite the availability of several 3D-structures of Sm-like archaeal proteins (SmAPs), their function has remained elusive. The aim of this study was to shed light on the function of SmAP1 and SmAP2 of the crenarchaeon Sulfolobus solfataricus (Sso). Using co-purification followed by RNASeq different classes of non-coding RNAs and mRNAs were identified that co-purified either with both paralogues or solely with Sso-SmAP1 or Sso-SmAP2. The large number of associated intron-containing tRNAs and tRNA/rRNA modifying RNAs may suggest a role of the two Sso-SmAPs in tRNA/rRNA processing. Moreover, the 3D structure of Sso-SmAP2 was elucidated. Like Sso-SmAP1, Ss...

Structure, 2015

Highlights d Calmodulin binds to plectin 1a via its N-terminal lobe in an extended conformation d... more Highlights d Calmodulin binds to plectin 1a via its N-terminal lobe in an extended conformation d The disordered N-ter tail of plectin 1a folds in an a helix upon calmodulin binding d Suitably positioned calmodulin displaces integrin b4 from complex with plectin 1a

PLoS ONE, 2012

In Escherichia coli the RNA chaperone Hfq is involved in riboregulation by assisting base-pairing... more In Escherichia coli the RNA chaperone Hfq is involved in riboregulation by assisting base-pairing between small regulatory RNAs (sRNAs) and mRNA targets. Several structural and biochemical studies revealed RNA binding sites on either surface of the donut shaped Hfq-hexamer. Whereas sRNAs are believed to contact preferentially the YKH motifs present on the proximal site, poly(A) 15 and ADP were shown to bind to tripartite binding motifs (ARE) circularly positioned on the distal site. Hfq has been reported to bind and to hydrolyze ATP. Here, we present the crystal structure of a C-terminally truncated variant of E. coli Hfq (Hfq 65) in complex with ATP, showing that it binds to the distal R-sites. In addition, we revisited the reported ATPase activity of full length Hfq purified to homogeneity. At variance with previous reports, no ATPase activity was observed for Hfq. In addition, FRET assays neither indicated an impact of ATP on annealing of two model oligoribonucleotides nor did the presence of ATP induce strand displacement. Moreover, ATP did not lead to destabilization of binary and ternary Hfq-RNA complexes, unless a vast stoichiometric excess of ATP was used. Taken together, these studies strongly suggest that ATP is dispensable for and does not interfere with Hfq-mediated RNA transactions.

Cell, 2014

The spectrin superfamily of proteins plays key roles in assembling the actin cytoskeleton in vari... more The spectrin superfamily of proteins plays key roles in assembling the actin cytoskeleton in various cell types, crosslinks actin filaments, and acts as scaffolds for the assembly of large protein complexes involved in structural integrity and mechanosensation, as well as cell signaling. a-actinins in particular are the major actin crosslinkers in muscle Z-disks, focal adhesions, and actin stress fibers. We report a complete high-resolution structure of the 200 kDa a-actinin-2 dimer from striated muscle and explore its functional implications on the biochemical and cellular level. The structure provides insight into the phosphoinositide-based mechanism controlling its interaction with sarcomeric proteins such as titin, lays a foundation for studying the impact of pathogenic mutations at molecular resolution, and is likely to be broadly relevant for the regulation of spectrinlike proteins.