Characterization of Deltoid, a chimeric protein containing the oligomerization site of hepatitis delta antigen

Both forms of the hepatitis delta antigen (HDAg) encoded by hepatitis delta virus are active only as oligomers. Previous studies showed that quadrin, a synthetic 50‐residue peptide containing residues 12–60 from the N‐terminus of HDAg, interferes with HDAg oligomerization, forms an α‐helical coiled coil in solution, and forms a novel square octamer in the crystal consisting of four antiparallel coiled‐coil dimers joined at the corners by hydrophobic binding of oligomerization sites located at each end of the dimers. We designed and synthesized deltoid (CH 3 CO‐[Cys23]HDAg‐(12‐27)‐seryl‐tRNA synthetae‐(59‐65)‐[Cys42]HDAg‐(34‐60)‐Tyr‐NH 2 ), a chimeric protein that structurally resembles one end of the quadrin dimer and contains a single oligomerization site. The 51‐residue chain of deltoid contains a seven‐residue α‐hairpin loop in place of the remainder of the quadrin dimer plus Cys12 and Cys31 for forming an intrachain disulfide bridge. Reduced, unbridged deltoid ( T m = 61°C, Δ G (H 2 O) = −1.7 kcal mol −1 ) was less stable to denaturation by heat or guanidine HCl than oxidized, intrachain disulfide‐bridged deltoid ( T m > 80°C, Δ G (H 2 O) = −2.6 kcal mol −1 ). Each form is an α‐helical dimer that reversibly dissociates into two monomers ( K d = 80 μ M ). © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 764–773, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com