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Fig. 2 | BMC Biology

Fig. 2

From: Defining rules governing recognition and Fc-mediated effector functions to the HIV-1 co-receptor binding site

Fig. 2

Molecular details of sulfoTyr (TYS) interactions with antibodies N12-i2, 412d, and the CCR5 co-receptor. N12-i2, CCR5, and 412d utilize two TYSs in gp120 binding (N12-i2: TYS100A and TYS100B; CCR5: TYS10 and TYS14 (PDB code: 6MET), and 412d: TYS100 and TYS100C (PDB code: 2QAD) with one (TYS100A of N12-i2, TYS14 of CCR5, and TYS100C of 412d) occupying the same binding pocket. The right panel shows the binding mode of TYS in the common binding pocket. TYS100A, TYS14, and TYS100C bind in a similar manner with the sulfate coordinated by hydrogen bonds (H-bonds) to Arg298, Ser300 (Thr303 in CCR5 and Asn300 in 412d), Asn301 (Asn302 in CCR5 and 412d) and to the main chain of Gly441. In addition, the aromatic ring of TYS is involved in hydrophobic interactions with Ile326 and Ile439, and hydrophobic and polar cation-π interactions with Pro438 and Asp440 (Lys440 in CCR5 and Arg440 in 412d). The 180° view shows the details of Asp98 in N12-i2 which occupies the same binding pocket as the second TYS of CCR5 and 412d (TYS10 and TYS100). Asp98 of N12-i2 buries 19 Å2 BSA in the N12-i2 Fab-gp12093TH057 coree-M48U1 complex and thus contributes significantly to N12-i2 binding. Asp98 forms a salt bridge to Arg327 with the aliphatic part of its side chain packing against Pro437 and Pro438. TYS10 of CCR5 forms H-bonds with the main chains of Ile423 and Gln422 and a salt bridge with Lys421 and Arg327. TYS100 of 412d is engaged in a main chain H-bond to Arg327 with its aromatic ring packed against the guanidinium group. TYS100 also forms a H-bond with Gln422 and a salt bridge with Arg419. The differences in this second sulfo-tyrosine binding pocket in CCR5 and 412d may be due to gp120 sequence differences in this region. gp120 numbering is relative to the HXBC2 reference sequence

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