Figure 2.

Cryo-EM Structure of the MT145K Trimer

(A) Schematic showing the MT145K SOSIP soluble trimer design from its full-length gp160 Env sequence. The gp120 constant (C1-C5) and variable (V1-V5) regions and the gp41 regions (fusion peptide, FP; heptad repeat, HR1 and HR2; membrane proximal external region, MPER; transmembrane, TM; and cytoplasmic tail, CT) are indicated. The N-linked glycan positions for each NXT or NXS residue are labeled according to the HIV HXB2 numbering scheme. The SOSIP trimer stabilizing modifications include (i) disulfide bond, A501C-T605C; (ii) R6 cleavage site; (iii) I559P; and (iv) 664-residue truncation in gp41 MPER. The substitution to incorporate a K residue at position 171 (Q171K) to gain binding for V2-apex iGL Abs is indicated in blue.

(B and C) Side (B) and top (C) views of the unliganded MT145K trimer model based on the cryo-EM density map at ∼4.1-Å resolution. Ribbon representations of the MT145K trimer spike, in which the subunits gp120 (cornflower blue) and gp41 (orange) are depicted on one protomer. The gp120 variable loops (V1-V5) positioned to the trimer periphery are depicted in different colors (V1, khaki; V2, red; V3, magenta; V4, yellow; and V5, chartreuse). The fusion peptide region of gp41 is shown in cyan. Glycan sugar residues modeled based on density are represented in forest green stick form.

(D) Superimposition of variable loops (V1-V5) and fusion peptide region for MT145K and unliganded HIV clade A BG505 (PDB: 4ZMJ) SOSIP trimers. The dotted lines indicate regions in the V loops or FP for which the observed electron density was absent or unclear.

(E) Structural comparison of gp41 regions of the MT145K (orange) and BG505 (gray) trimers. The gp41 structural elements overall show a similar arrangement except for the fusion peptide region (colored cyan on MT145K and pink on BG505), which is exposed on the BG505 trimer but remains hidden in a pocket inside the MT145K trimer.