The crystal structure of V3 resolved recently shows that V3 protrudes~30 Å from the CD4-bound gp120 core, and this extended structure can be divided into three regions: the base (residues 1-8 and [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] , the stem (9-14 and 18-24) and the crown (residues 15-17) (residue numbering w.r.t. V3) [23, 24] . The V3 loop of gp120 is highly antigenic in humans [25] [26] [27] [28] , and was previously recognized as the principal neutralizing domain of HIV-1 [29] . However its role was shown to be restricted to type specific viruses [30, 31] and such an observation was supported by the extensive sequence variation in V3 from different viral isolates [32, 33] . Given the critical interaction with the co-receptors (CXCR4 or CCR5) on host cells, V3 conventionally must retain structurally conserved elements required for binding [34, 35] . More recently, studies have revealed that the V3 domain possesses conserved structural motifs despite the sequence variation, and is often accessible on the virus surface as a target for bNAbs [21, [36] [37] [38] .