期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：6
DOI：10.1073/pnas.2111745119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Biomineralization, the process by which elaborate three-dimensional structures are built out of organic and inorganic molecules, is central to health and survival of many organisms. In some magnetotactic bacteria, the growth of magnetosome membranes is closely correlated to the progression of mineral formation. However, the molecular mechanisms of such regulation are not clear. We show that the serine protease MamE links magnetosome membrane growth to the controlled production of magnetite nanoparticles through the processing of mineral-associated MamD protein. Our results indicate that membrane growth directly controls mineral growth and shed light on how an organelle’s size can determine its physiological output. Manipulation of the MamE pathway may also open the door for control of nanoparticle size in future biotechnological applications.
Magnetosomes are lipid-bound organelles that direct the biomineralization of magnetic nanoparticles in magnetotactic bacteria. Magnetosome membranes are not uniform in size and can grow in a biomineralization-dependent manner. However, the underlying mechanisms of magnetosome membrane growth regulation remain unclear. Using cryoelectron tomography, we systematically examined mutants with defects at various stages of magnetosome formation to identify factors involved in controlling membrane growth. We found that a conserved serine protease, MamE, plays a key role in magnetosome membrane growth regulation. When the protease activity of MamE is disrupted, magnetosome membrane growth is restricted, which, in turn, limits the size of the magnetite particles. Consistent with this finding, the upstream regulators of MamE protease activity, MamO and MamM, are also required for magnetosome membrane growth. We then used a combination of candidate and comparative proteomics approaches to identify Mms6 and MamD as two MamE substrates. Mms6 does not appear to participate in magnetosome membrane growth. However, in the absence of MamD, magnetosome membranes grow to a larger size than the wild type. Furthermore, when the cleavage of MamD by MamE protease is blocked, magnetosome membrane growth and biomineralization are severely inhibited, phenocopying the MamE protease-inactive mutant. We therefore propose that the growth of magnetosome membranes is controlled by a protease-mediated switch through processing of MamD. Overall, our work shows that, like many eukaryotic systems, bacteria control the growth and size of biominerals by manipulating the physical properties of intracellular organelles.
