Crystal structure of 05.GC.w13.01 and 05.GC.w13.02 in complex with A/California/04/2009 (CA04) H1N1 HA and A/Vietnam/1203/04 (Viet04) H5N1 HA. The CA04 H1N1 HA is shown as a molecular surface in white for HA1 and gray for HA2. Residues involved in side-chain and backbone interactions between HA and Fab are represented in white (HA1) and gray (HA2) sticks. HCDR and LCDR represent CDRs in the heavy (H) and light (L) chains. Hydrogen bonds and salt bridges are indicated with black dashes. Fab residues are in Kabat numbering throughout. 05.GC.w13.01-H1 is in sand, 05.GC.w13.02-H1 in teal, 05.GC.w13.02-H5 in orange, and CR9114 in maroon. Fabs and HAs are shown in backbone cartoons with interacting side chains in sticks. For clarity, HA and Fab residues are colored with black and red numbers, respectively. (A) Structural comparison of HFR1-HCDR1 in 05.GC.w13.01-H1, 05.GC.w13.02-H1, and 05.GC.w13.02-H5. (B) Sequence comparisons of the IGHV1-69*12 germline, 05.GC.w2.3C10, 05.GC.w13.01, 05.GC.w13.02, and CR9114. Yellow highlights two critical motifs in HFR1 and HCDR2 in each Fab. (C) Interactions between the TF motif and the upper pocket of HA in each complex are shown. Residues involved in the interactions within this pocket are depicted in sticks. (D) The critical motif for residues 53 and 54 in HCDR2 for each Fab is shown: IV in VF in 05.GC.w2.3C10, 05.GC.w13.01, IL in 05.GC.w13.02, and IF in CR9114. This motif binds to the lower pocket in the HA stem. See also Fig. S4 and Tables S1 and S2.