The 3ʹUUUOH RNA-binding cleft in the La-module of HsLa. (A) Global view of the 3ʹUUUOH binding site in HsLa (2VOD). The La-module is in grey in both surface and cartoon representations with LaM helices α1, α1ʹ and α2 highlighted in different shades of blue. The strands of the RRM1 β-sheet are in shades of olive (β1), brick (β2), purple (β3) and pink (β4). (B) Zoomed-in view in the same orientation showing U−2 residing deep in the binding crevice formed by the LaM and RRM1 interface, while U−1 stacks on α2 of LaM, and U−3 stacks on U−1. (C) Details of the interaction, highlighting the stacking ladder of U−3 and U−1 on F35, and the stacking of U−2 on Y23, as well as the H-bonds of D33 with the two terminal hydroxyls (dotted lines). Dotted lines also identify the specific H-bonds between U−2 to the main chain of I140 in the β2-strand of RRM1 and to the side chain of Q20 from α1 of the LaM domain. The figure was prepared using PyMOL (https://pymol.org/2/)