KARGAS Vasileios

A polar SxxS motif drives assembly of the transmembrane domains of Toll-like receptor 4

Published date : 22 Jul 2017

Like all members of the Toll-like receptor (TLR) family, TLR4 comprises of a large ectodomain (ECD) involved in ligand recognition at the cell-surface, and a cytosolic Toll/interleukin-1 receptor (TIR) signalling domain, linked by a lipid membrane-anchored transmembrane (TM) domain (TMD).

type
Journal Paper
journal
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2017 Jul 22;1859(10):2086-2095. doi: 10.1016/j.bbamem.2017.07.010
Impact Factor
3.498

Full-length, Oligomeric Structure of Wzz Determined by Cryoelectron Microscopy Reveals Insights into Membrane-Bound States

Published date : 20 Apr 2017

Wzz is an integral inner membrane protein involved in regulating the length of lipopolysaccharide O-antigen glycans and essential for the virulence of many Gram-negative pathogens. In all Wzz homologs, the large periplasmic domain is proposed to be anchored by two transmembrane helices, but no information is available for the transmembrane and cytosolic domains. Here we have studied purified oligomeric Wzz complexes using cryoelectron microscopy and resolved the transmembrane regions within a semi-continuous detergent micelle.

type
Journal Paper
journal
Structure, 2017 May 2;25(5):806-815. e3. doi: 10.1016/j.str.2017.03.017
Impact Factor
5.618

The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6

Published date : 10 Aug 2016

Hereditary porphyrias are caused by mutations in genes that encode haem biosynthetic enzymes with resultant buildup of cytotoxic metabolic porphyrin intermediates. A longstanding open question is why the same causal porphyria mutations exhibit widely variable penetrance and expressivity in different individuals. Here we show that severely affected porphyria patients harbour variant alleles in the ABCB6 gene, also known as Lan, which encodes an ATP-binding cassette (ABC) transporter. Plasma membrane ABCB6 exports a variety of disease-related porphyrins.

type
Journal Paper
journal
Nature Communications 7, 2016, Article no: 12353, doi:10.1038/ncomms12353
Impact Factor
11.05

The role of protein-protein interactions in Toll-like receptor function

Published date : 02 Jul 2015

As part of the innate immune system, the Toll-like receptors (TLRs) represent key players in the first line of defense against invading foreign pathogens, and are also major targets for therapeutic immunomodulation. TLRs are type I transmembrane proteins composed of an ectodomain responsible for ligand binding, a single-pass transmembrane domain, and a cytoplasmic Toll/Interleukin-1 receptor (TIR) signaling domain.

type
Journal Paper
journal
Progress in Biophysics and Molecular Biology, Vol. 119, Issue 1, October 2015, Pages 72–83. doi: 10.1016/j.pbiomolbio.2015.06.021