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. Author manuscript; available in PMC: 2015 Feb 16.
Published in final edited form as: Annu Rev Nutr. 2014 May 16;34:281–303. doi: 10.1146/annurev-nutr-071812-161220

Figure 2. The FA binding site on CD36 and its access to a transport tunnel within the molecule.

Figure 2

The structure of human CD36 exofacial domain (K36 – G436) was modeled using the Phyre2 prediction server (41) based on the recently reported crystal structure of the CD36 family member LIMP2 (68). 98% of residues modeled at >90% confidence. Fig 2-A: Ribbon model of CD36 structure highlighting the SSO-target residue K164. Also highlighted is K334 a secondary and rare SSO target (44). Figure 2-B: Detail of the CD36 structure showing the FA (oleic acid) docking site using the SwissDock server (30) (Full fitness -2409.97 kcal/mol; estimated ΔG -8.59kcal/mol). Figure 2-B: Surface hydrophobicity is indicated, with blue denoting hydrophilic residues and red hydrophobic residues. The FA is shown to dock within a hydrophobic pocket at the top of CD36 near helix 5 with the FA carboxylic tail in close proximity to lysine 164 (green residue), previously shown to bind the oleate derivative SSO (44). The FA pocket is shaped into a sliding groove that heads towards the tunnel present within the protein structure, modeled based on the one identified by the crystal structure of LIMP2 (68). The glutamic acid residue 335 (magenta color) is positioned at the site of FA entry into the tunnel. K164 might be important for correct positioning of the FA within the pocket possibly allowing it to slide into the tunnel, and for inducing a conformational change in the protein that initiates signaling. Fig. 2-C: A vertical slice through the CD36 modeled structure showing the rear side of the tunnel which is formed mainly by beta strand 21 and outlets close to the plasma membrane. The arrows show predicted direction of FA transport. Our working hypothesis is that the FA interacts with K164 within the hydrophobic groove which positions it to slide with the acyl chain leading the way into the tunnel. The outlet of the tunnel is likely buried in the charged layer of the membrane which would facilitate transport of the hydrophobic acyl chain through the bilayer.