Science - 6 December 2019

Steichenet al.,Science 366 , eaax4380 (2019) 6 December 2019 7of13

HCDR3

AKDFLLSTSGYLSYGDYYYYGMDV

ARSWALFCSSTSCTNYYYYYGMDV

TTDIGYGDYLRSLDYYYYYGMDV

ARDQIREEWELLPEYYYYGMDV

AREESIVLMVYAIPADKDAFDI

ARKGPEGDGYNWELGTLYYFDY

ARQKVDYDFWSGYPAGYGMDV

ARDPTPNYYDSSGYWVGAFDI

ARDRGREWELESYYYYYYMDV

AKDIESRYFDWDNYYYYGMDV

ARDVSRNWGWEEDYYYYGMDV

ARVKYSSSWYVDDYYYGMDV

ARGDLYYYDSSGYYYYGMDV

ARAWDYDYVWGSYGVDGMDV

AKGPQHYYDSSGYPEYYFDY

ARDGTLYYYDSSGYYSYFDY

ARDRDSYYYDSSGYSDYFDY

ARGSVYYYDSSGYFWDAFDI

ARDATMSIAPNYYYYYGMDV

AREWDGGYSGYDSGDWYFDL

HCDR3

BG18-mat ARNAI RIYGVVALGEWFHYGMDV 23

BG18-iGL 0 ARNAITIFGVVIIGEYYYYGMDV 23

HMP1 AREGFTIFGVVTFSEGYYYGMDV 23

HMP68 TRAPITIFGVVQLGDYYYYYMDV 23

HMP69 ARDRITIFGVVIIGENYYYGMDV 23

A

B

C

D

Fig. 4. Sequence and structural characterization of type I and type II
BG18-like naïve antibodies isolated by N332-GT Env trimers.(A)HCDR3
sequence and gene segment assignmentsforthreetypeIBG18-likenaïve
human precursor antibodies. V, D, and J gene segments are colored blue, red,
and green, respectively. Single-letter abbreviations for amino acid residues
areasfollows:A,Ala;C,Cys;D,Asp;E,Glu;F,Phe;G,Gly;H,His;I,Ile;K,Lys;
L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and
Y, Tyr. (B) HCDR3 sequence and gene segment assignments for 20 type II
BG18-like precursor antibodies. (C) Cryo-EM structural analysis of type I

(HMP1) and type II (HMP42) precursor antibody LC interactions with

N332-GT5 compared with BG18 iGL LC interactions with N332-GT2. Gp120 is

colored gray, and the LCs are colored cyan, yellow, and blue for BG18 iGL,

HMP1, and HMP42, respectively. (D) Cryo-EM structural analysis of type I and

type II precursor HCDR3 interactions with N332-GT5 compared with HCDR3

interactions for BG18+MD39 and BG18iGL+N332-GT2 complexes. Gp120

is colored gray with conserved residues (or the corresponding germline-

targeting amino acids) near the base of V3 colored red as in Fig. 1A.

Glycans are shown as green sticks.

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