The beta subunit of DNA pol III provides for the remarkable processivity of the holoenzyme during replication. The subunit is a ring-shaped clamp which embraces DNA in a central 35 angstrom hole and tethers the remainder of pol III to the template <>. The beta subunit is a homodimer of two beta monomers (each contains 366 amino acids;Mr=40.6 kD) which form the two halves of the clamp <>. The dimer interface is a novel continuation, across the monomer boundry, of a beta sheet structure, indistinguishable from intra-monomer beta
sheets <>. Four strong hydrogen bonds link beta strands across each of the two interfaces.

Hydrophobic interactions of amino acid sidechains are also important in stabilizing the dimer interface. R groups of Phe-106 and Ile-108 of one monomer pack against Ile-272 and Leu-273 of the other and form a hydrophobic core <>. Additionally, there are four pairs of potential ionically-bonded anino acid side chains accessible to solvent (water) <>. Two potential ion pairs (Arg-96, Glu-300 and Arg-103, Glu-304) are inaccessible to solvent and so might form particularly strong ionic bonds <>.

The beta monomers are arranged in a head-to-tail (N-C-->N-C-->) orientation which yields non-symmetric faces of the dimeric
ring <>. The two carboxy termini (spacefill) project from the face which binds the remainder of the Pol III holoenzyme <>. Note that this face contains six prominent loops which are well-suited to bind other pol III subunits <>.

Three domains with nearly identical structure (not amino acid sequence) comprise each monomer. The amino, central, and carboxy domains each harbor an outer layer of two beta sheets which support two inner alpha helices. Thus, the core of the dimeric clamp is lined with 12 alpha helices
(2 helices/domain x 3 domains/monomer x 2 monomers) <>.

The 35 Angstrom hole of the Beta dimer is large enough to accomodate double helical nucleic acid with little steric hinderance as shown here for B-DNA (~20 Angstrom diameter). The tilt of the 12 central alpha helices is similar due to the symmetrical arrangement of the six domains <>. The axis of each alpha helix can be seen to be perpendicular to the sugar-phosphate backbone of both major and minor DNA grooves when the DNA is modeled perpendicular to the plane of the beta clamp ring (a seemingly valid assumption) <>.

This arrangement is in contrast to other DNA-binding proteins that commonly contain alpha helices which lie parallel to the nucleic acid backbone and recognize and fit into the major groove. The perpendicular orientation of the beta clamp helices and DNA backbone seems designed to prevent access of the protein to either DNA groove and therefore to facilitate rapid sliding of the clamp along the DNA axis. These principles hold for interaction with A-form DNA-RNA duplexes (~25 Angstrom diameter), found at the site of initial clamping of the Beta subunit at the RNA-primed template of the start of an Okazaki fragment <>.

Kong, X-P., Onrust, R., O'Donnell, M., and J. Kuriyan (1992). Three-Dimensional Structure of the Beta Subunit of E. coli DNA Polymerase III Holoenzyme: A Sliding DNA Clamp. Cell 69: 425-437.