X-ray crystal structure of phosphorylated human
SLBP. (A) Schematic
showing the domain organization of human SLBP (hSLBP) and Drosophila SLBP (dSLBP). The RNA binding domain is designated
the “L-motif” and is followed by an acidic region, rich
in Asp and Glu residues, that is also phosphorylated. The N-terminal
domain is involved in translation activation (TAD). Phosphorylation
sites that have been mapped in vivo(76,80,124) are indicated. (B) The T171
phosphorylated SLBP L-motif is shown with a characteristic L-shape
as seen in the crystal structure of the hSLBP/histone mRNA/3′hExo
ternary complex (PDB code 4QOZ). The fold consists of three α-helices connected
by a 20-residue flexible loop that has the site of phosphorylation
(shown in stick). Hydrophobic residues at the junction of the helices
are shown in yellow (inset). (C) Hydrogen bonding interactions mediated
by the phosphothreonine with R163, R169, K146, Y151, and W190 (via
a water molecule) are shown. The structured loop that is disordered
in the unphosphorylated SLBP structure is fully ordered in phosphorylated
SLBP. The unphosphorylated structure is shown in blue and the phosphorylated
structure in red ribbon. (D) Residues in helix-2 and the structured
loop that undergo a conformational change upon SLBP phosphorylation
and have been implicated in RNA processing are highlighted.