A5048866718- Protein Kinase Regulation and GTPase Signaling
- PI3K/AKT/mTOR signaling in cancer
- Cellular transport and secretion
- Laser-induced spectroscopy and plasma
- Bacterial Genetics and Biotechnology
- Calibration and Measurement Techniques
- Surface Roughness and Optical Measurements
- Distributed and Parallel Computing Systems
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- Protein Structure and Dynamics
- Laser-Plasma Interactions and Diagnostics
- Protein Tyrosine Phosphatases
- Receptor Mechanisms and Signaling
- Bacteriophages and microbial interactions
- DNA Repair Mechanisms
- Biochemical and Molecular Research
- Optical Polarization and Ellipsometry
- RNA and protein synthesis mechanisms
- Pancreatic function and diabetes
- Distributed systems and fault tolerance
- Melanoma and MAPK Pathways
- Cellular Mechanics and Interactions
- Toxoplasma gondii Research Studies
Max Perutz Labs
2015-2024
Vienna Biocenter
2015-2023
Medical University of Vienna
2015-2023
University of Vienna
2019-2020
The University of Texas at Austin
2019
University of Southampton
2001-2013
National Institutes of Health
1991-2013
UK Research and Innovation
2007-2012
MRC Laboratory of Molecular Biology
2004-2010
National Institute of Diabetes and Digestive and Kidney Diseases
2010
Significance Akt is a paradigmatic lipid-activated kinase, which frequently hyperactivated in human cancer. In the absence of PI(3,4,5)P 3 or PI(3,4)P 2 , maintained an inactive conformation by inhibitory interaction between its membrane-binding PH domain and kinase domain. Here, we describe conformational changes associated with binding to leading disruption PH−kinase interface, consequent activation protein kinases. Intriguingly, find that reversal those promotes inactivation phosphatases....
3-phosphoinositide-dependent kinase 1 (PDK1) is an essential serine/threonine protein kinase, which plays a crucial role in cell growth and proliferation. It often referred to as 'master' due its ability activate at least 23 downstream kinases implicated various signaling pathways. In this study, we have elucidated the mechanism of phosphoinositide-driven PDK1 auto-activation. We show that trans-autophosphorylation mediated by PIP
Significance Akt is an essential protein kinase that controls cell growth, survival, and metabolism. activated by the lipid second messengers PIP 3 PI(3,4)P 2 phosphorylation. However, relative contributions of binding phosphorylation to activity in are controversial. Here, we have determined structure autoinhibited Akt1, which reveals how lipid-binding PH domain maintains inactive conformation absence . Despite stoichiometric phosphorylation, adopts with low basal Our work mechanistic basis...
Phosphorylation of proteins is a ubiquitous mechanism regulating their function, localization, or activity. Protein kinases, enzymes that use ATP to phosphorylate protein substrates are, therefore, powerful signal transducers in eukaryotic cells. The phosphoryl-transfer universally conserved among which necessitates the tight regulation kinase activity for orchestration cellular processes with high spatial and temporal fidelity. In response stimulus, many kinases enhance own by...
Abstract The Rho-associated coiled-coil kinases (ROCK) are essential regulators of the actin cytoskeleton; however, structure a full-length ROCK is unknown and mechanisms by which its kinase activity controlled not well understood. Here we determine low-resolution human ROCK2 using electron microscopy, revealing it to be constitutive dimer, 120 nm in length, with long tether linking membrane-binding domains. We find, contrast previous reports, that does appear directly regulated binding...
Prokaryotic chromosomes and plasmids encode partitioning systems that are required for DNA segregation at cell division. The plasmid loci two proteins, ParA ParB, a cis-acting centromere-like site denoted parS. chromosomally encoded homologues of Soj Spo0J, play an active role in chromosome during bacterial division sporulation. Spo0J is DNA-binding protein binds to parS sites vivo. We have solved the X-ray crystal structure C-terminally truncated (amino acids 1-222) from Thermus...
The phosphoinositide 3-kinase (PI3K) pathway is a major regulator of cell and organismal growth. Consequently, hyperactivation PI3K its downstream effector kinase, Akt, observed in many human cancers. Pleckstrin homology domain leucine-rich repeat-containing protein phosphatases (PHLPP), two paralogous members the metal-dependent phosphatase family, have been reported as negative regulators Akt signaling and, therefore, tumor suppressors. However, stoichiometry identity bound metal ion(s),...
This paper discusses methods of predicting the BRDF smooth surfaces from profile measurements their surface finish. The conversion optical data to at same wavelength is essentially independent scattering models, while mechanical measurements, and scaling in general, are model dependent. Procedures illustrated for several surfaces, including two recent HeNe round robin, results compared with measured data. Reasonable agreement found except which involve significant isolated defects poorly sampled
MORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic distribution, being found in both prokaryotes eukaryotes. Despite this ubiquity, they remain poorly characterised at structural functional level compared to other common repeats. In terms, are often assumed be lipid-binding modules that mediate membrane targeting. We addressed putative activity by focusing on protein composed solely of repeats— Trypanosoma brucei MORN1. Surprisingly, no evidence for...
The Tec kinases, closely related to Src family are essential for lymphocyte function in the adaptive immune system. Whilst and Abl kinases regulated by tail phosphorylation N-terminal myristoylation respectively, notable absence of either regulatory element. We have found that inactive conformations kinase Itk preferentially bind ADP over ATP, stabilising both proteins. demonstrate adopts same conformation as autoinhibited is independent its C-terminal tail. Allosteric activation depends...