The DC-SIGNR length variants with 7-, 6-, and 5-neck repeats jumped to contact with the neoglycolipid layers from distances of respectively D J, 7 = 30.6 ( 1. 1 nm for the 7-, 6-, and 5-repeat proteins. The greater uncertainty in determinations of D eq is due to the low force values relative to the measurement uncertainty of (0.03 and the shallow slopes near D eq , especially with the 5-repeat variant (cf. Figure 3C ). In these measurements, Biochemistry ARTICLE the average value of D eq is less than D C by 2.1 ( 0.5 nm (Table 1) due to the relatively soft repulsion at D < D eq . In the majority of the measurements, at D < D C the force curve is nearly flat for ∼1.5 nm (Figure 2 ), before increasing more steeply. This jump-to-contact is evidence of functionally active protein because the mechanical instability, which underlies the jump-in requires an attractive force between the ligand and protein monolayers. Protein inactivation would ablate the attraction. All three DC-SIGNR variants exhibit this jump-to-contact behavior, which was also observed in comparable experiments with DC-SIGN. 18 Furthermore, the observation that both D C and D eq are significantly less than D T , despite the presence of the bulky glycan on the target membrane, is attributed to flexibility in the DC-SIGN structure that enables the proteins to undergo a conformational change upon binding the target neoglycolipid. 18 Such protein flexibility would increase the reaction cross section of the CRDs and hence the range of interaction of the CRDs as well as their ability to bind ligands at different, lateral spatial distributions on target surfaces. Both DC-SIGN and all three DC-SIGNR variants exhibit this flexibility, although it is less apparent with the 5-repeat form of DC-SIGNR, due to the weaker attraction.