Kneale G G
Biophysics Laboratories, University of Portsmouth, U.K.
J Mol Biol. 1994 Oct 14;243(1):1-5. doi: 10.1006/jmbi.1994.1624.
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 M2S. 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 interacting 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 S-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.
I型DNA甲基转移酶是复杂的多亚基酶，可在不对称二分DNA识别序列的每一半中的特定碱基上进行甲基化。特异性（S）亚基包含两个相应的DNA序列识别结构域，以及一些与两个修饰（M）亚基相互作用以形成M2S形式的三聚体酶的保守区域。长期以来，亚基以假对称方式与DNA相互作用的方式尚不清楚。对S亚基内部序列重复的分析表明，中央保守结构域与N和C末端附近的序列之间存在显著同源性。基于这种“分裂重复”，提出了该亚基结构域的“环状”组织方式，为与M亚基和靶DNA序列相互作用提供了所需的对称性。在提出的模型中，一个M亚基与S亚基的N和C末端保守区域相互作用，从而使它们紧密靠近。第二个M亚基与中央保守结构域中的重复序列进行等效接触。该模型提出了一种更通用的方案，通过与其他亚基进行等效接触，在具有内部重复序列的蛋白质亚基上施加假二元对称性。
