Search results for "Transmembrane"

Classes of non-conventional tetraspanins defined by alternative splicing

2019

AbstractTetraspanins emerge as a family of membrane proteins mediating an exceptional broad diversity of functions. The naming refers to their four transmembrane segments, which define the tetraspanins‘ typical membrane topology. In this study, we analyzed alternative splicing of tetraspanins. Besides isoforms with four transmembrane segments, most mRNA sequences are coding for isoforms with one, two or three transmembrane segments, representing structurally mono-, di- and trispanins. Moreover, alternative splicing may alter transmembrane topology, delete parts of the large extracellular loop, or generate alternative N- or C-termini. As a result, we define structure-based classes of non-con…

O1‐06‐07: Misprocessing of Multiple Transmembrane Substrates Reveals Gamma‐Secretase Dysfunction in Both Familial and Sporadic Alzheimer's Diseases

2009

Solution NMR structure of aD,L-alternating oligonorleucine as a model of ?-helix

2001

beta-Helix structures are of particular interest due to their capacity to form transmembrane channels with different transport properties. However, the relatively large number of beta-helices configurations does not allow a direct conformational analysis of beta-helical oligopeptides. A synthetic alternating D,L-oligopeptide with twelve norleucines (XIIMe) has been used as a model to get insight in the conformational features of beta-helix structures. The spatial configuration of XIIMe in solution has been determined by NMR. An extensive set of distances (nuclear Overhauser effect) and dihedral (J coupling constants) constraints have been included in molecular dynamics calculations. The NMR…

In silico strategy for detection of target candidates for antibody therapy of solid tumors

2008

In contrast to earlier attempts for the identification of target candidates suitable for monoclonal antibody (mAb) based cancer therapies we concentrated on highly selective lineage-specific genes additionally preserved or even overexpressed in orthotopic cancers. In a script aided workflow we reduced all human entries of the RefSeq mRNA database to those encoding transmembrane domain bearing gene products and subjected them to BLAST analysis against the human EST database. All BLAST results were validated in a gene centric way allowing two types of data curation prior to expression profiling of matching ESTs in selected healthy tissues: (i) exclusion of questionable ESTs arising e.g. from …

6-mercaptopurine and 9-(2-phosphonyl-methoxyethyl) adenine (PMEA) transport altered by two missense mutations in the drug transporter gene ABCC4

2008

Multiple drug resistance protein 4 (MRP4, ABCC4) belongs to the C subfamily of the ATP-binding cassette (ABC) transporter superfamily and participates in the transport of diverse antiviral and chemotherapeutic agents such as 6-mercaptopurine (6-MP) and 9-(2-phosphonyl methoxyethyl) adenine (PMEA). We have undertaken a comprehensive functional characterization of protein variants of MRP4 found in Caucasians and other ethnicities. A total of 11 MRP4 missense genetic variants (nonsynonymous SNPs), fused to green fluorescent protein (GFP), were examined in Xenopus laevis oocytes for their effect on expression, localization, and function of the transporter. Radiolabeled 6-MP and PMEA were chosen…

The Tobacco mosaic virus movement protein associates with but does not integrate into biological membranes

2014

Plant positive-strand RNA viruses require association with plant cell endomembranes for viral translation and replication, as well as for intra- and intercellular movement of the viral progeny. The membrane association and RNA binding of the Tobacco mosaic virus (TMV) movement protein (MP) are vital for orchestrating the macromolecular network required for virus movement. A previously proposed topological model suggests that TMV MP is an integral membrane protein with two putative -helical transmembrane (TM) segments. Here we tested this model using an experimental system that measured the efficiency with which natural polypeptide segments were inserted into the ER membrane under conditions…

The putative sponge aggregation receptor. Isolation and characterization of a molecule composed of scavenger receptor cysteine-rich domains and short…

1998

Porifera (sponges) are the oldest extant metazoan phylum. Dissociated sponge cells serve as a classic system to study processes of cell reaggregation. The reaggregation of dissociated cells is mediated by an extracellularly localized aggregation factor (AF), based on heterophilic interactions of the third order; the AF bridges two cells by ligating a cell-surface-bound aggregation receptor (AR). In the present study we report cloning, expression and immunohistochemical localization of a polypeptide from the marine sponge Geodia cydonium, which very likely represents the AR. The presumed AR gene gives rise to at least three forms of alternatively spliced transcripts of 6.5, 4.9 and 3.9 kb, a…

Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes.

2020

Background: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. Methods: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. Findings: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammatio…

Peripherin-2 couples rhodopsin to the CNG channel in outer segments of rod photoreceptors.

2014

Outer segments (OS) of rod photoreceptors are cellular compartments specialized in the conversion of light into electrical signals. This process relies on the light-triggered change in the intracellular levels of cyclic guanosine monophosphate (cGMP), which in turn controls the activity of cyclic nucleotide-gated (CNG) channels in the rod OS plasma membrane. The rod CNG channel is a macromolecular complex that in its core harbors the ion-conducting CNGA1 and CNGB1a subunits. To identify additional proteins of the complex that interact with the CNGB1a core subunit we applied affinity purification of mouse retinal proteins followed by mass spectrometry. In combination with in vitro and in viv…

A transmembrane serine residue in the Rot1 protein is essential for yeast cell viability

2014

Polar residues are present in TM (transmembrane) helices and may influence the folding or association of membrane proteins. In the present study, we use an in vivo approach to analyse the functional and structural roles for amino acids in membrane-spanning motifs using the Rot1 (reversal of Tor2 lethality 1) protein as a model. Rot1 is an essential membrane protein in Saccharomyces cerevisiae and it contains a single TM domain. An alanine insertion scanning analysis of this TM helix revealed that the integrity of the central domain is essential for protein function. We identified a critical serine residue inside the helix that plays an essential role in maintaining cell viability in S. cere…