Avtor/Urednik		Manček-Keber, Mateja
Naslov		LPS-vezavni proteini: analiza lastosti in interakcij z endotoksinom
Prevedeni naslov		LPS-binding proteins: analysis of their properties and interactions with endotoxin
Tip		monografija
Kraj izdaje		Ljubljana
Založnik		Univerza v Ljubljani, Medicinska fakulteta
Leto izdaje		2005
Obseg		str. 109
Jezik		slo
Abstrakt		Bacterial infection activates host's innate immune response. Bacterial motifs, which are recognized by the innate immune response, have been called pathogen-associated molecular patterns (PAMPs). Bacterial blood invasion and septicemia can lead to a condition called sepsis or septic shock, which can be deadly, and develops when the initial, appropriate response to bacteria becomes amp(ified and harmful. Most cases of septic shock are caused by Gram-negative bacteria. In Gram-negative bacteria endotoxin (chemically lipopolysaccharide - LPS) from the outer membrane has a dominant role. Understanding the mechanisms of interaction between LPS and LPS-binding proteins is of a high importance not only for basic science, but mainly for treatment and prevention of sepsis. In blood circle LPS is bound by extracellular proteins LBP and CD14. LPS is then transmitted to TLR4, a transmembrane receptor, which transmitts the signal into the cell. MD-2 binds to extracellular domain of TLR4 and is essential for the LPS signaling. It has been shown that MD-2 is capable of binding LPS itself. By using a secondary structure predition method we have identified a 1 ` amino acid amphipatic region of human MD-2 and in vitro neutralization of LPS by this peptide was observed. Furthermore the peptide inhibited growth of Gram-negative and some Gram-positive bacteria. We prepared a tertiary structure model of MD-2 based on the known structure of homologous protein Der p 2. The model was confirmed with site-directed MD-2 mutants and bacterially expressed recombinant MD-2 (bMD-2). Mutations of each of the two basic clusters Lys89Ala/Arg90Ala/Lys91 and Lys125AlalLys128A1a, which are situated at the entrance of the proposed hydrophobic pocket, decreased MD-2 activity. (Abstract truncated at 2000 characters).
Deskriptorji		SEPSIS ENDOTOXINS POLYSACCHARIDES, BACTERIAL INTERLEUKIN-6 POINT MUTATION RECOMBINANT PROTEINS BINDING SITES PROTEIN BINDING CHROMATOGRAPHY, AFFINITY FLOW CYTOMETRY PROTEIN STRUCTURE, SECONDARY SPECTROMETRY, FLUORESCENCE ENZYME-LINKED IMMUNOSORBENT ASSAY