Characterization of 05.GC.w2.3C10 and 05.GC.w13.02 in complex with A/California/04/2009 (CA04) H1N1 HA. 05.GC.w2.3C10 and 05.GC.w13.02 are in yellow and teal, respectively. For clarity, HA and Fab residues are colored with black and red numbers, respectively. (A) Structural comparison of the binding of HFR1-HCDR1 with 05.GC.w2.3C10 and 05.GC.w13.02. The red circles indicate the TF motif in 05.GC.w2.3C10 that is lower than the corresponding motif in 05.GC.w13.02. (B) Detailed molecular interactions between 05.GC.w13.02 (left) and 05.GC.w2.3C10 (right) with CA04 HA. (C) The role of the hydrophobic HFR3 Leu74 in 05.GC.w13.02 (left), and the different binding of Ser74 in 05.GC.w2.3C10 (middle). The right panel shows that F29 from the TS motif in 05.GC.w2.3C10 occupies the middle hydrophobic groove. (D) Binding affinity of 05.GC.w13.02 with deletions of residues 31 and 32 to H1 (A/Michigan/45/2015) using BLI. See also Fig. S4 and Tables S1 and S2.