Dr. Anna Arbuzova
Profil
Forschungsthemen1
Supramolekulare Organisation von Cholesterol-modifizierten Nukleosiden in Mikroröhren: Charakterisierung und Funktionalisierung
Quelle ↗Förderer: DFG Eigene Stelle (Sachbeihilfe) Zeitraum: 06/2011 - 09/2015 Projektleitung: Dr. Anna Arbuzova, Prof. Dr. rer. nat. Andreas Herrmann
Mögliche Industrie-Partner10
Stand: 26.4.2026, 19:48:44 (Top-K=20, Min-Cosine=0.4)
- DYnamic control in hybrid plasmonic NAnopores: road to next generation multiplexed single MOlecule detectionP61.3%
- DYnamic control in hybrid plasmonic NAnopores: road to next generation multiplexed single MOlecule detection
- 4 Treffer56.0%
- Systematic Models for Biological Systems Engineering Training NetworkP56.0%
- Systematic Models for Biological Systems Engineering Training Network
- 4 Treffer56.0%
- Systematic Models for Biological Systems Engineering Training NetworkP56.0%
- Systematic Models for Biological Systems Engineering Training Network
Protatuans-Etaireia Ereynas Viotechologias Monoprosopi Etaireia Periorisments Eythinis
P3 Treffer56.0%- Systematic Models for Biological Systems Engineering Training NetworkP56.0%
- Systematic Models for Biological Systems Engineering Training Network
- 4 Treffer56.0%
- Systematic Models for Biological Systems Engineering Training NetworkP56.0%
- Systematic Models for Biological Systems Engineering Training Network
- 23 Treffer55.9%
- Engineering of New-Generation Protein Secretion SystemsP55.9%
- Engineering of New-Generation Protein Secretion Systems
- 23 Treffer55.9%
- Engineering of New-Generation Protein Secretion SystemsP55.9%
- Engineering of New-Generation Protein Secretion Systems
- 23 Treffer55.9%
- Engineering of New-Generation Protein Secretion SystemsP55.9%
- Engineering of New-Generation Protein Secretion Systems
- 6 Treffer55.5%
- Integrated Self-Assembled SWITCHable Systems and Materials: Towards Responsive Organic Electronics – A Multi-Site Innovative Training Action (iSwitch)P55.5%
- Integrated Self-Assembled SWITCHable Systems and Materials: Towards Responsive Organic Electronics – A Multi-Site Innovative Training Action (iSwitch)
- 21 Treffer55.5%
- Integrated Self-Assembled SWITCHable Systems and Materials: Towards Responsive Organic Electronics – A Multi-Site Innovative Training Action (iSwitch)P55.5%
- EU: Bottom-Up Generation of atomicalLy Precise syntheTIc 2D MATerials for High Performance in Energy and Electronic Applications – A Multi-Site Innovative Training Action (ULTIMATE)P51.1%
- Integrated Self-Assembled SWITCHable Systems and Materials: Towards Responsive Organic Electronics – A Multi-Site Innovative Training Action (iSwitch)
Publikationen25
Top 25 nach Zitationen — Quelle: OpenAlex (BAAI/bge-m3 embedded für Matching).
Biochemical Journal · 302 Zitationen · DOI
The proteins of the MARCKS (myristoylated alanine-rich C kinase substrate) family were first identified as prominent substrates of protein kinase C (PKC). Since then, these proteins have been implicated in the regulation of brain development and postnatal survival, cellular migration and adhesion, as well as endo-, exo- and phago-cytosis, and neurosecretion. The effector domain of MARCKS proteins is phosphorylated by PKC, binds to calmodulin and contributes to membrane binding. This multitude of mutually exclusive interactions allows cross-talk between the signal transduction pathways involving PKC and calmodulin. This review focuses on recent, mostly biophysical and biochemical results renewing interest in this protein family. MARCKS membrane binding is now understood at the molecular level. From a structural point of view, there is a consensus emerging that MARCKS proteins are "natively unfolded". Interestingly, domains similar to the effector domain have been discovered in other proteins. Furthermore, since the effector domain enhances the polymerization of actin in vitro, MARCKS proteins have been proposed to mediate regulation of the actin cytoskeleton. However, the recent observations that MARCKS might serve to sequester phosphatidylinositol 4,5-bisphosphate in the plasma membrane of unstimulated cells suggest an alternative model for the control of the actin cytoskeleton. While myristoylation is classically considered to be a co-translational, irreversible event, new reports on MARCKS proteins suggest a more dynamic picture of this protein modification. Finally, studies with mice lacking MARCKS proteins have investigated the functions of these proteins during embryonic development in the intact organism.
Biochemical Journal · 222 Zitationen · DOI
The proteins of the MARCKS (myristoylated alanine-rich C kinase substrate) family were first identified as prominent substrates of protein kinase C (PKC). Since then, these proteins have been implicated in the regulation of brain development and postnatal survival, cellular migration and adhesion, as well as endo-, exo- and phago-cytosis, and neurosecretion. The effector domain of MARCKS proteins is phosphorylated by PKC, binds to calmodulin and contributes to membrane binding. This multitude of mutually exclusive interactions allows cross-talk between the signal transduction pathways involving PKC and calmodulin. This review focuses on recent, mostly biophysical and biochemical results renewing interest in this protein family. MARCKS membrane binding is now understood at the molecular level. From a structural point of view, there is a consensus emerging that MARCKS proteins are ‘natively unfolded'. Interestingly, domains similar to the effector domain have been discovered in other proteins. Furthermore, since the effector domain enhances the polymerization of actin in vitro, MARCKS proteins have been proposed to mediate regulation of the actin cytoskeleton. However, the recent observations that MARCKS might serve to sequester phosphatidylinositol 4,5-bisphosphate in the plasma membrane of unstimulated cells suggest an alternative model for the control of the actin cytoskeleton. While myristoylation is classically considered to be a co-translational, irreversible event, new reports on MARCKS proteins suggest a more dynamic picture of this protein modification. Finally, studies with mice lacking MARCKS proteins have investigated the functions of these proteins during embryonic development in the intact organism.
Biophysical Journal · 183 Zitationen · DOI
Journal of Biological Chemistry · 176 Zitationen · DOI
Both the myristoylated alanine-rich protein kinase C substrate protein (MARCKS) and a peptide corresponding to its basic effector domain, MARCKS-(151-175), inhibit phosphoinositide-specific phospholipase C (PLC)-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP(2)) in vesicles (Glaser, M., Wanaski, S., Buser, C. A., Boguslavsky, V., Rashidzada, W., Morris, A., Rebecchi, M., Scarlata, S. F., Runnels, L. W., Prestwich, G. D., Chen, J., Aderem, A., Ahn, J., and McLaughlin, S. (1996) J. Biol. Chem. 271, 26187-26193). We report here that adding 10-100 nm MARCKS-(151-175) to a subphase containing either PLC-delta or -beta inhibits hydrolysis of PIP(2) in a monolayer and that this inhibition is due to the strong binding of the peptide to PIP(2). Two direct binding measurements, based on centrifugation and fluorescence, show that approximately 10 nm PIP(2), in the form of vesicles containing 0.01%, 0.1%, or 1% PIP(2), binds 50% of MARCKS-(151-175). Both electrophoretic mobility measurements and competition experiments suggest that MARCKS-(151-175) forms an electroneutral complex with approximately 4 PIP(2). MARCKS-(151-175) binds equally well to PI(4,5)P(2) and PI(3,4)P(2). Local electrostatic interactions of PIP(2) with MARCKS-(151-175) contribute to the binding energy because increasing the salt concentration from 100 to 500 mm decreases the binding 100-fold. We hypothesize that the effector domain of MARCKS can bind a significant fraction of the PIP(2) in the plasma membrane, and release the bound PIP(2) upon interaction with Ca(2+)/calmodulin or phosphorylation by protein kinase C.
Biochemistry · 162 Zitationen · DOI
We have studied the binding of peptides containing both basic and aromatic residues to phospholipid vesicles. The peptides caveolin(92-101) and MARCKS(151-175) both contain five aromatic residues, but have 3 and 13 positive charges, respectively. Our results show the aromatic residues insert into the bilayer and anchor the peptides weakly to vesicles formed from the zwitterionic lipid phosphatidylcholine (PC). Incorporation of a monovalent acidic lipid (e.g., phosphatidylserine, PS) into the vesicles enhances the binding of both peptides via nonspecific electrostatic interactions. As predicted from application of the Poisson-Boltzmann equation to atomic models of the peptide and membranes, the enhancement is larger (e.g., 10(4)- vs 10-fold for 17% PS) for the more basic MARCKS(151-175). Replacing the five Phe with five Ala residues in MARCKS(151-175) decreases the binding to 10:1 PC/PS vesicles only slightly (6-fold). This result is also consistent with the predictions of our theoretical model: the loss of the attractive hydrophobic energy is partially compensated by a decrease in the repulsive Born/desolvation energy as the peptide moves away from the membrane surface. Incorporating multivalent phosphatidylinositol 4, 5-bisphosphate (PIP(2)) into PC vesicles produces dramatically different effects on the membrane binding of the two peptides: 1% PIP(2) enhances caveolin(92-101) binding only 3-fold, but increases MARCKS(151-175) binding 10(4)-fold. The strong interaction between the effector region of MARCKS and PIP(2) has interesting implications for the cellular function of MARCKS.
Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · 139 Zitationen · DOI
Current topics in membranes · 84 Zitationen · DOI
Angewandte Chemie International Edition · 82 Zitationen · DOI
Anchoring for DNA: A lipophilic oligonucleotide consisting of 21 thymidine units and two lipophilic nucleotides L was synthesized and bound to vesicular surfaces (see fluorescence image). The membrane-bound oligonucleotide binds complementary DNA strands by formation of Watson–Crick base pairs. The lipid-anchored oligonucleotide is preferentially enriched in liquid-disordered membrane domains.
Journal of Biological Chemistry · 82 Zitationen · DOI
Membrane binding of the myristoylated alanine-rich C kinase substrate (MARCKS) requires both its myristate chain and basic "effector" region. Previous studies with a peptide corresponding to the effector region, MARCKS-(151-175), showed that the 13 basic residues interact electrostatically with acidic lipids and that the 5 hydrophobic phenylalanine residues penetrate the polar head group region of the bilayer. Here we describe the kinetics of the membrane binding of fluorescent (acrylodan-labeled) peptides measured with a stopped-flow technique. Even though the peptide penetrates the polar head group region, the association of MARCKS-(151-175) with membranes is extremely rapid; association occurs with a diffusion-limited association rate constant. For example, kon = 10(11) M-1 s-1 for the peptide binding to 100-nm diameter phospholipid vesicles. As expected theoretically, kon is independent of factors that affect the molar partition coefficient, such as the mole fraction of acidic lipid in the vesicle and the salt concentration. The dissociation rate constant (koff) is approximately 10 s-1 (lifetime = 0.1 s) for vesicles with 10% acidic lipid in 100 mM KCl. Ca2+-calmodulin (Ca2+.CaM) decreases markedly the lifetime of the peptide on vesicles, e.g. from 0.1 to 0.01 s in the presence of 5 micrM Ca2+.CaM. Our results suggest that Ca2+.CaM collides with the membrane-bound MARCKS-(151-175) peptide and pulls the peptide off rapidly. We discuss the biological implications of this switch mechanism, speculating that an increase in the level of Ca2+-calmodulin could rapidly release phosphatidylinositol 4, 5-bisphosphate that previous work has suggested is sequestered in lateral domains formed by MARCKS and MARCKS-(151-175).
Biochimica et Biophysica Acta (BBA) - Biomembranes · 73 Zitationen · DOI
Biochimica et Biophysica Acta (BBA) - Biomembranes · 65 Zitationen · DOI
Langmuir · 63 Zitationen · DOI
The development of targeted and triggerable delivery systems is of high relevance for anticancer therapies. We report here on reduction-sensitive liposomes composed of a novel multifunctional lipidlike conjugate, containing a disulfide bond and a biotin moiety, and natural phospholipids. The incorporation of the disulfide conjugate into vesicles and the kinetics of their reduction were studied using dansyl-labeled conjugate 1 in using the dansyl fluorescence environmental sensitivity and the Förster resonance energy transfer from dansyl to rhodamine-labeled phospholipids. Cleavage of the disulfide bridge (e.g., by tris(2-carboxyethyl)phosphine (TCEP), dithiothreitol (DTT), l-cysteine, or glutathione (GSH)) removed the hydrophilic headgroup of the conjugate and thus changed the membrane organization leading to the release of entrapped molecules. Upon nonspecific uptake of vesicles by macrophages, calcein release from reduction-sensitive liposomes consisting of the disulfide conjugate and phospholipids was more efficient than from reduction-insensitive liposomes composed only of phospholipids. The binding of streptavidin to the conjugates did not interfere with either the subsequent reduction of the disulfide bond of the conjugate or the release of entrapped molecules. Breast cancer cell line BT-474, overexpressing the HER2 receptor, showed a high uptake of the reduction-sensitive doxorubicin-loaded liposomes functionalized with the biotin-tagged anti-HER2 antibody. The release of the entrapped cargo inside the cells was observed, implying the potential of using our system for active targeting and delivery.
The Journal of Physical Chemistry B · 63 Zitationen · DOI
Cholesterol-based lipophilic oligonucleotides incorporated into lipid membranes were studied using solid-state NMR, differential scanning calorimetry, and fluorescence methods. Lipophilic oligonucleotides can be used to build nanotechnological structures on membrane surfaces, taking advantage of the specific Watson-Crick base pairing. We used a cholesteryl-TEG anchor first described by Pfeiffer and Hook (J. Am. Chem. Soc. 2004, 126, 10224-10225). The cholesterol-based anchor molecules were found to incorporate well into lipid membranes without disturbing the bilayer structure and dynamics. In contrast to cholesterol, which is known to induce significant condensation of the membrane lipids, the cholesteryl-TEG anchor does not display this property. When the cholesteryl-TEG moiety was covalently bound to an oligonucleotide, the resulting lipophilic DNA molecules inserted spontaneously into lipid membranes without altering their structure. The duplex formed by two complementary cholesteryl-TEG oligonucleotides had increased thermodynamic stability compared to the same oligonucleotides without the anchor, both in solution and incorporated into lipid membranes. Since the cholesteryl-TEG anchor lacks the characteristic properties of cholesterol, oligonucleotides modified with this anchor are equally distributed between liquid-disordered and liquid-ordered domains in "raft" forming membranes. As an example of an application of these lipophilic oligonucleotides, cholesteryl-TEG-DNA was incorporated into supported lipid bilayers formed on polyelectrolyte-coated silica microparticles. The modified oligonucleotides were stably inserted into the lipid membrane and retained their recognition properties, therefore enabling further functionalization of the particles.
Journal of the American Chemical Society · 61 Zitationen · DOI
Lipid domains in mammalian plasma membranes serve as platforms for specific recruitment or separation of proteins involved in various functions. Here, we have applied this natural strategy of lateral separation to functionalize lipid membranes at micrometer scale in a switchable and reversible manner. Membrane-anchored peptide nucleic acid and DNA, differing in their lipophilic moieties, partition into different lipid domains in model and biological membranes. Separation was visualized by hybridization with the respective complementary fluorescently labeled DNA strands. Upon heating, domains vanished, and both lipophilic nucleic acid structures intermixed with each other. Reformation of the lipid domains by cooling led again to separation of membrane-anchored nucleic acids. By linking appropriate structures/functions to complementary strands, this approach offers a reversible tool for triggering interactions among the structures and for the arrangement of reactions and signaling cascades on biomimetic surfaces.
Microelectrophoresis of a Bilayer-Coated Silica Bead in an Optical Trap: Application to Enzymology
2001Biophysical Journal · 61 Zitationen · DOI
Biochimica et Biophysica Acta (BBA) - Biomembranes · 58 Zitationen · DOI
Journal of Molecular Biology · 40 Zitationen · DOI
Journal of the American Chemical Society · 39 Zitationen · DOI
Lateral partitioning of lipid-modified molecules between liquid-disordered (ld) and liquid-ordered (lo) domains depends on the type of lipid modification, presence of a spacer, membrane composition, and temperature. Here, we show that the lo domain partitioning of the palmitoylated peptide nucleic acid (PNA) can be influenced by formation of a four-component complex with the ld domain partitioning tocopherol-modified DNA: the PNA-DNA complex partitioned into the ld domains. Enzymatic cleavage of the DNA linker led to the disruption of the complex and restored the initial distribution of the lipophilic nucleic acids into the respective domains. This modular system offers strategies for dynamic functionalization of biomimetic surfaces, for example, in nanostructuring and regulation of enzyme catalysis, and it provides a tool to study the molecular basis of controlled reorganization of lipid-modified proteins in membranes, for example, during signal transduction.
Advances in Colloid and Interface Science · 37 Zitationen · DOI
Small · 31 Zitationen · DOI
Microscopic colloidal particles allow a precise regulation of chemical reactions in time and place. A controlled assembly of multiple layers of intact lipid vesicles on a solid support provided by layer-by-layer particles functionalized by a covalent attachment of DNA oligonucleotides is reported (see image). Lipophilic complementary oligonucleotides are incorporated into lipid vesicles. Fusion of liposomes and release can be triggered.
Synthesis of Nucleosides with 2′‐Fixed Lipid Anchors and Their Behavior in Phospholipid Membranes
2008European Journal of Organic Chemistry · 23 Zitationen · DOI
Abstract Various new nucleosides bearing one or two lipophilic groups at the 2′‐position have been synthesized. The lipophilic substituents were attached to a 2′‐hydroxy, 2′‐amino, or 2′‐thio function. These lipophilic nucleosides anchor in large unilamellar POPC vesicles serving as phospholipid membrane models. The insertion of these molecules into the membranes was investigated by NMR techniques. For comparison, nucleosides with two or three lipophilic groups at the 2′‐, 3′‐, or 5′‐positions have also been studied.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Chemical Communications · 19 Zitationen · DOI
We describe the formation of lipid microtubes from a novel cholesterol-modified nucleoside in binary mixture with phospholipids. Stable cylindrical structures with an outer diameter of 2-3 microm and a length of 20-40 microm were formed. By varying the preparation conditions, thinner tubules with nanometre-scale diameters could also be obtained.
European Journal of Organic Chemistry · 18 Zitationen · DOI
Abstract A straightforward synthesis of 2′‐functionalized uridines was developed based on a Cu‐catalyzed cycloaddition of 2′‐azido‐2′‐deoxyuridine and functionalized alkynes. The functions comprise biochemically important groups such as lipids, a fluorescent marker (Cy5 analogue), pentaacetylglucose, lysine and biotin, and are linked to the 2′‐position of uridine by a 1,2,3‐triazole ring. A number of NMR spectroscopic investigations revealed that the lipidated 2′‐triazolyl‐2′‐deoxyuridines anchor themselves in the phospholipid membranes without affecting the molecular order in the double layers; the polar moieties – uracil, ribose and triazole – are located in the lipid/water interface of the membrane.
Soft Matter · 13 Zitationen · DOI
Structural and dynamic properties of membranes composed of phosphatidylcholine (PC) and phosphatidylserine (PS) on layer-by-layer (LbL) polyelectrolyte coated particles were investigated using solid-state nuclear magnetic resonance (NMR) and fluorescence methods. These spherically supported membranes showed structural, dynamic, and elastic properties similar to free-standing membranes as proved by 31P and 2H NMR. Small differences between behaviour of PC and PS on LbL support due to interaction with the polyelectrolyte were observed. Fluorescence lifetime imaging microscopy (FLIM) using 7-nitro-2-1,3-benzoxadiazol (NBD) labeled PC and PS showed a stronger impact of the outermost polyelectrolyte (PAH) on the fluorescence lifetimes of NBD-PS compared to NBD-PC. Although small defects in nm range allowing passage of Mn2+ to both layers of the membrane coat were present, a rather homogeneous coating observed by fluorescence microscopy, complete fluorescence recovery after photobleaching, and NMR results reveal that somewhat continuous lipid bilayers were formed around the LbL particles.
Steinkopff eBooks · 13 Zitationen · DOI
The apparent pore formation induced by polistes Mastoparan (MPP) and Mastoparan-X (MPX) in the membrane of large unilamellar POPC vesicles has been investigated. The time-course of the process was monitored by the fluorescence signal F(t) reflecting the release of the marker substance carboxyfluorescein, which is entrapped in the vesicles at a self-quenching concentration. The data were analyzed according to a recently proposed theory allowing a quantitative evaluation of the pore kinetics and the mode of dye release. A mode of graded release was found for both peptides. The average dye retention factor of a single pore turned out to be ρ ∼ 0.70 ± 0.05 for MPP and ρ ∼ 0.55 ± 0.05 for MPX. The measured fluorescence signal F(t) has been converted into the average retention function R(t), i.e., the fraction of marker retained inside the liposomes after a given time of efflux. Then the pore formation rate per liposome could be determined and fitted to a pertinent time function. The relevant kinetic parameters are discussed in relation to the concentration of actually bound peptide.
Kooperationen0
Bestätigte Forscher↔Partner-Paare aus HU-FIS — Gold-Standard-Positive für das Matching.
Aus HU-FIS sind keine Kooperationen für diese Person gemeldet.
Stammdaten
Identität, Organisation und Kontakt aus HU-FIS.
- Name
- Dr. Anna Arbuzova
- Titel
- Dr.
- Fakultät
- Präsidialbereich
- Institut
- Stabsstelle Berlin University Alliance / Matters of Activity
- Arbeitsgruppe
- Matters of Activity
- Telefon
- +49 30 2093-66301
- HU-FIS-Profil
- Quelle ↗
- Zuletzt gescrapt
- 26.4.2026, 01:01:59