RT Journal Article
SR Electronic
T1 Tunable hetero-assembly of a plant pseudoenzyme-enzyme complex
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 717082
DO 10.1101/717082
A1 Irina V. Novikova
A1 Mowei Zhou
A1 Chen Du
A1 Marcelina Parra
A1 Doo Nam Kim
A1 Zachary L. VanAernum
A1 Jared B. Shaw
A1 Hanjo Hellmann
A1 Vicki H. Wysocki
A1 James E. Evans
YR 2020
UL http://biorxiv.org/content/early/2020/05/09/717082.abstract
AB Pseudoenzymes have emerged as key regulatory elements in all kingdoms of life despite being catalytically non-active. Yet many factors defining why one protein is active while its homolog is inactive remain uncertain. For pseudoenzyme-enzyme pairs, the similarity of both subunits can often hinder conventional characterization approaches. In plants, a pseudoenzyme PDX1.2 positively regulates vitamin B6 production by association with its active catalytic homologs such as PDX1.3 through an unknown mechanism. Here we used an integrative experimental approach to learn that such pseudoenzyme-enzyme pair associations result in hetero-complexes of variable stoichiometry, which are unexpectedly tunable. We also present the atomic structure of the PDX1.2 pseudoenzyme as well as the population averaged PDX1.2-PDX1.3 pseudoenzyme-enzyme pair. Finally, we dissected hetero-dodecamers of each stoichiometry to understand the arrangement of monomers in the hetero-complexes and identified symmetry- imposed preferences in PDX1.2-PDX1.3 interactions. Our results provide a new model of pseudoenzyme-enzyme interactions and their native heterogeneity.Competing Interest StatementThe authors have declared no competing interest.