STABILITY OF THE DYSTROPHIN ROD DOMAIN FOLD - EVIDENCE FOR NESTED REPEATING UNITS

An examination of fragments of the human dystrophin rod domain, corres ponding to a single structural repeating unit, showed that a critical chain length, defined with a precision of one residue at the C-termina l end, is required for formation of the native tertiary fold, We repor t here that extending the chain by six residues beyond this minimum re sults in a large increase in conformational stability, This is not rel ated to a change in association state of the polypeptide. The results support the conjecture that successive repeating units in the rod doma in of the spectrinlike proteins form a nested structure, in which the N-terminal part of the three-helix bundle of one repeat packs into the overlapping structure of the preceding repeat, This would be expected to affect functional characteristics related to flexibility of the dy strophin rod domain.