Search results for "Ankyrin"
showing 6 items of 16 documents
Effects of ligand binding on the mechanical properties of ankyrin repeat protein gankyrin.
2012
Ankyrin repeat proteins are elastic materials that unfold and refold sequentially, repeat by repeat, under force. Herein we use atomistic molecular dynamics to compare the mechanical properties of the 7-ankyrin-repeat oncoprotein Gankyrin in isolation and in complex with its binding partner S6-C. We show that the bound S6-C greatly increases the resistance of Gankyrin to mechanical stress. The effect is specific to those repeats of Gankyrin directly in contact with S6-C, and the mechanical ‘hot spots’ of the interaction map to the same repeats as the thermodynamic hot spots. A consequence of stepwise nature of unfolding and the localized nature of ligand binding is that it impacts on all as…
Molecular and topological membrane folding determinants of transient receptor potential vanilloid 2 channel.
2015
Transient Receptor Potential (TRP) channels are related to adaptation to the environment and somatosensation. The transient receptor potential vanilloid (TRPV) subfamily includes six closely evolutionary related ion channels sharing the same domain organization and tetrameric arrangement in the membrane. In this study we have characterized biochemically TRPV2 channel membrane protein folding and transmembrane (TM) architecture. Deleting the first N-terminal 74 residues preceding the ankyrin repeat domain (ARD) show a key role for this region in targeting the protein to the membrane. We have demonstrated the co-translational insertion of the membrane-embedded region of the TRPV2 and its disp…
Molecular Evolution of Apoptotic Pathways: Cloning of Key Domains from Sponges (Bcl-2 Homology Domains and Death Domains) and Their Phylogenetic Rela…
2000
Cells from metazoan organisms are eliminated in a variety of physiological and pathophysiological processes by apoptosis. In this report, we describe the cloning and characterization of molecules from the marine sponges Geodia cydonium and Suberites domuncula, whose domains show a high similarity to those that are found in molecules of the vertebrate Bcl-2 superfamily and of the death receptors. The Bcl-2 proteins contain up to four Bcl-2 homology regions (BH). Two Bcl-2-related molecules have been identified from sponges that are provided with two of those regions, BH1 and BH2, and are termed Bcl-2 homology proteins (BHP). The G. cydonium molecule, BHP1_GC, has a putative size of 28,164, w…
Genome-wide significant association of ANKRD55 rs6859219 and multiple sclerosis risk.
2013
Multiple sclerosis (MS) is a genetically complex disease that shares a substantial proportion of risk loci with other autoimmune diseases.1 Along these lines, ANKRD55 , originally implicated in rheumatoid arthritis, was recently reported as a potential novel MS risk gene (rs6859219, p=1.9×10−7).2 Here, we comprehensively validated this effect in independent datasets comprising 8846 newly genotyped subjects from Germany and France as well as 5003 subjects from two genome-wide association studies (GWAS). Upon meta-analysis of all available data (19 686 subjects), ANKRD55 rs6859219 now shows compelling evidence for association with MS at genome-wide significance (OR=1.19, p=3.1×10−11). Our stu…
Direct binding of Magi2 to the USH1G protein SANS links the periciliary USH protein network to endocytosis
2012
The human Usher syndrome (USH) is the most common form of combined deaf-blindness. The encoded molecules are integrated into protein networks by scaffolds including the USH1G protein SANS (scaffold protein containing ankyrin repeats and SAM domain). Previous studies indicated SANS´ participation in vesicle transport and cargo handover at the periciliary region of photoreceptor cells. To decipher the precise cellular role of SANS, we searched for interacting partners. Therefore we adopted a yeast-2-hybrid screen of a retinal cDNA library using SANS´ C-terminus as bait. Amongst others we identified the MAGUK protein Magi2 (membrane-associated guanylate kinase inverted-2) as putative binding p…
Direct interaction of the Usher syndrome 1G protein SANS and myomegalin in the retina
2011
Contains fulltext : 96822.pdf (Publisher’s version ) (Closed access) The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically heterogeneous with at least 11 chromosomal loci assigned to 3 clinical types, USH1-3. We have previously demonstrated that all USH1 and 2 proteins in the eye and the inner ear are organized into protein networks by scaffold proteins. This has contributed essentially to our current understanding of the function of USH proteins and explains why defects in proteins of different families cause very similar phenotypes. We have previously shown that the USH1G protein SANS (scaffold protein containing ankyrin repeat…