Membrane interaction (Figure 2B). As with HIV, a hydrophobic cavity formed by the side chains of helices h1 to h4 is observed in the FIV p15 protein (Figure 2B). Our docking studies demonstrated that a myristoyl group can be placed in this cavity with its carboxyl end in the vicinity of the Nterminus of p15, providing the local adjustment of residues from helices h1, h2 and h4 (Trp9, Phe35, Ile39, n-Phenylpiperazine-1-carboxamide Ile53, and Phe90, Figure 2C). These residues are located at the same positions as the residues interacting with the N-terminal myristoyl of the HIV MA (Ser9, Ile34, Ser38, Leu51 and Leu85, respectively [21]). The estimated binding free energy of the myristoyl group is similar for FIV and HIV (-2.9 kcal/mol and -3.7 kcal/mol, respectively). One striking feature, when the myristoyl group is inserted in the hydrophobic pocket of FIV p15, is the predicted motion of Trp9 and Ile53, which rotate from their initial position (Figure 2C). Of interest, our docking experiments revealed a second putative binding site for the myristoyl group that wraps around the first turn of helix h1 (Figure 2D) in a groove located at the surface of the protein (Figure 2E). This location involves the interaction of themyristoyl group with residues Trp9, Ala12, Arg15, Glu55 and Leu95 of helix h1 and loops l2 and l4. FIV p15, despite having a low sequence similarity with HIV, EIAV and SIV MA (18 , 17 and 15 sequence identities, respectively) is strikingly similar in structure to these lentiviral matrix PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/20618955 proteins and can be superposed to each with a root mean square deviation (RMSD) of 1.9 ? 2.5 ? and 2.1 ?between C pairs, respectively (Table 2). However, the superimposition of the lentiviral MA structure reveals a major difference around the C-terminal end Fmoc-D-Asp-OtBu of MA (Figure 3). The C-terminal end of FIV p15 is mainly unstructured and extended (Figures 2 and 3), whereas a long helix h5 is observed in HIV p17 (Figure 3A), and a short -hairpin is reported in SIV MA (Figure 3B). The C-terminal end of EIAV p15 is not visible in the electron density maps and is absent from itsTable 2 Structural comparisons with other lentiviral matrix proteinsProtein EIAV MA HIV MA SIV MAPDB ID 1HEK 1HIW 1ECWRMSD1 2.5 ?1.9 ?2.1 ?N2 align 99 101seq3 17 18Root Mean Square Deviation calculated between C-atoms of matched residues. 2 Number of aligned residues after structure superimposition. 3 Sequence identity.Serri e et al. Retrovirology 2013, 10:64 http://www.retrovirology.com/content/10/1/Page 6 ofFigure 3 Structural comparison of four lentiviral matrix protein. The superimposition of the matrix proteins of FIV (red) with (A) HIV (PDB ID: 1HIW, blue), (B) SIV (PDB ID: 1ECW, green) and (C) EIAV (PDB ID: 1HEK, yellow) matrix proteins. The N- and C-termini are indicated, and the helices are numbered h1 to h5 as in Figure 2A. Black arrows highlight the structural differences at the C-terminal end of the matrix proteins.structure (Figure 3C). Another difference is the presence of longer loops in FIV as compared with EIAV, HIV and SIV because of insertions in the FIV sequence (Figure 4). As these loops are important to the stabilization of HIV and SIV trimers, the longer PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/11834444 loops may be related to the differences observed in the FIV p15 oligomerization. There are 6 conserved residues between the proteins (Figure 2-dioxaborolane 3-Fluoro-5-iodobromobenzene Cyclobutylboronic acid 4, black squares), most of which are within the helical sections of the molecule, and they may be responsible for maintaining the characteristic matrix architecture. Finally, we can observe in the.