Polymerase associated factor 1 complex (Paf1C) broadly influences gene
expression by regulating chromatin structure and the recruitment of
RNA-processing factors during transcription elongation. The Plus3 domain of the
Rtf1 subunit mediates Paf1C recruitment to genes by binding a repeating domain
within the elongation factor Spt5 (suppressor of Ty). Here we provide a
molecular description of this interaction by reporting the structure of human
Rtf1 Plus3 in complex with a phosphorylated Spt5 repeat. We find that Spt5
binding is mediated by an extended surface containing phosphothreonine
recognition and hydrophobic interfaces that interact with residues outside the
Spt5 motif. Changes within these interfaces diminish binding of Spt5 in vitro
and chromatin localization of Rtf1 in vivo. The structure reveals the basis for
recognition of the repeat motif of Spt5, a key player in the recruitment of gene
regulatory factors to RNA polymerase II.
