SYMMETRICAL MODEL FOR THE DOMAIN-STRUCTURE OF TYPE-I DNA METHYLTRANSFERASES

Type I DNA methyltransferases are complex multisubunit enzymes that methylate a specific base in each half of an asymmetric bipartite DNA recognition sequence. The specificity (S) subunit contains two corresponding DNA sequence recognition domains, plus a number of conserved regions which interact with two modification (M) subunits to form a trimeric enzyme of the form M(2)S. The way in which the subunits interact with DNA in a pseudo-symmetric fashion has long been unclear. Analysis of internal sequence repeats in the S-subunit shows the occurrence of significant homologies between the central conserved domain and sequences near the N and C termini. On the basis of this ''split repeat'', a ''circular'' organisation of the domains of this subunit is proposed that provides the required symmetry for inter acting with the M-subunits and with the target DNA sequence. In the proposed model, one M-subunit interacts with the N and C-terminal conserved regions of the X-subunit, which are thereby brought into close proximity The second M-subunit makes equivalent contacts with repeated. sequences in the central conserved domain. The model suggests a more general scheme for the imposition of pseudo-dyad symmetry on protein subunits that have internal repeats by making equivalent contacts with additional subunits.