The Structural Basis of Recognition of LPS by Receptors of the Innate Immune System

• Applicant: Professor Dr. Wolfram Welte
• Subject Area: Immunology
• Term: from 2002 to 2004
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5357480

The proposed project aims to understand at an atomic level the pattern recognition processes which mediate the lipopolysaccharide (LPS) induced stimulation of the innate immune response. Our serependipituous determination of the first atomic structure of LPS in complex with a membrane protein [] indicated a surface pattern of amino acids suitable for binding LPS [] which may be used in the receptor molecules of the innate immune response (LBP, CD14 and the Toll-like receptor TLR4) as well. These cell-surface receptors some of which may also mediate adhesion [] remind us to our work on the structure and mechanism of Axonin-1-mediated axonal adhesion []. Stimulated by these previous structure determinations and the expertise we have accumulated in the crystallization of this kind of proteins we propose here to launch an extended set of crystallization attempts with extracellular fragments from LBP, CD14 and TLR4 alone, in complex with LPS and as ternary complexes containing LPS.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1110: Innate Immunity
• Major Instrumentation: HPLC-System zur Methoden- und Prozessentwicklung, Scale-up und Produktion im Pilotmaßstab
• Instrumentation Group: 1350 Flüssigkeits-Chromatographen (außer Aminosäureanalysatoren 317), Ionenaustauscher
• Participating Person: Professor Dr. Kay Diederichs