Dynamics on human Toll‐like receptor 4 complexation to MD‐2: The coreceptor stabilizing function. Issue 2 (February 2015)

• Record Type: Journal Article
• Authors: de Aguiar, Carla; Costa, Mauricio G. S.; Verli, Hugo
• Is Part Of: Proteins. Volume 83:Issue 2(2015)
• Page Start: 373
• Page End: 382
• Publication Date: 2015-02
• Subjects: Proteins -- Periodicals; Proteins -- Periodicals; 572.6
• DOI: 10.1002/prot.24739
• Languages: English
• ISSNs: 0887-3585

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>The interaction between human Toll‐like receptor 4 (hTLR4) and its coreceptor, myeloid differentiation factor 2 (MD‐2), is important in Gram‐negative bacteria lipopolysaccharide (LPS) recognition. In this process, MD‐2 recognizes LPS and promotes the dimerization of the complex hTLR4–MD‐2–LPS, triggering an intracellular immune signaling. In this study, we employed distinct computational methods to explore the dynamical properties of the hTLR4–MD‐2 complex and investigated the implications of the coreceptor complexation to the structural biology of hTLR4. We characterized both global and local dynamics of free and MD‐2 complexed hTLR4, in both (hTLR4–MD‐2)₁ and (hTLR4–MD‐2)₂ states. Both molecular dynamics and normal mode analysis reveled a stabilization of the terminal regions of hTLR4 upon complexation to MD‐2. We are able to identify conserved important residues involved on the hTLR4–MD‐2 interaction dynamics and disclose C‐terminal motions that may be associated to the signaling process upon oligomerization. Proteins 2015; 83:373–382. © 2014 Wiley Periodicals, Inc.</p> </abstract>