Polar Interactions at the Dimer-Dimer Interface of Methionine Adenosyltransferase MAT I Control Tetramerization.

ABSTRACT: Catalytic MATα1 subunits associate into kinetically distinct homo-dimers (MAT III) and homo-tetramers (MAT I) that synthesize S-adenosylmethionine in the adult liver. Pathological reductions in S-adenosylmethionine levels correlate with MAT III accumulation; thus, it is important to know the determinants of dimer-dimer associations. Here, polar interactions (<3.5 Å) at the rat MAT I dimer-dimer interface were disrupted by site-directed mutagenesis. Heterologous expression rendered decreased soluble mutant MATα1 levels that appeared mostly as dimers. Substitutions at the B1-B2 or B3-C1 β-strand loops, or changes in charge on helix α2 located behind, induced either MAT III or MAT I accumulation. Notably, double mutants combining neutral changes on helix α2 with substitutions at either β-stra

SUBMITTER: Sanchez-Perez GF 

PROVIDER: S-EPMC8703375 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature