The majority of eukaryotic pre-mRNAs are processed by 3'-end cleavage and 
polyadenylation, although in metazoa the replication-dependent histone mRNAs are 
processed by 3'-end cleavage but not polyadenylation. The macromolecular complex 
responsible for processing both canonical and histone pre-mRNAs contains the 
approximately 1160-residue protein Symplekin. Secondary-structural prediction 
algorithms identified putative HEAT domains in the 300 N-terminal residues of 
all Symplekins of known sequence. The structure and dynamics of this domain were 
investigated to begin elucidating the role Symplekin plays in mRNA maturation. 
The crystal structure of the Drosophila melanogaster Symplekin HEAT domain was 
determined to 2.4 A resolution with single-wavelength anomalous dispersion 
phasing methods. The structure exhibits five canonical HEAT repeats along with 
an extended 31-amino-acid loop (loop 8) between the fourth and fifth repeat that 
is conserved within closely related Symplekin sequences. Molecular dynamics 
simulations of this domain show that the presence of loop 8 dampens correlated 
and anticorrelated motion in the HEAT domain, therefore providing a neutral 
surface for potential protein-protein interactions. HEAT domains are often 
employed for such macromolecular contacts. The Symplekin HEAT region not only 
structurally aligns with several established scaffolding proteins, but also has 
been reported to contact proteins essential for regulating 3'-end processing. 
Together, these data support the conclusion that the Symplekin HEAT domain 
serves as a scaffold for protein-protein interactions essential to the mRNA 
maturation process.