TY - JOUR A1 - Hackenberg, Claudia A1 - Hakanpaeae, Johanna A1 - Cai, Fei A1 - Antonyuk, Svetlana A1 - Eigner, Caroline A1 - Meissner, Sven A1 - Laitaoja, Mikko A1 - Janis, Janne A1 - Kerfeld, Cheryl A. A1 - Dittmann, Elke A1 - Lamzin, Victor S. T1 - Structural and functional insights into the unique CBS-CP12 fusion protein family in cyanobacteria JF - Proceedings of the National Academy of Sciences of the United States of America N2 - Cyanobacteria are important photosynthetic organisms inhabiting a range of dynamic environments. This phylum is distinctive among photosynthetic organisms in containing genes encoding uncharacterized cystathionine beta-synthase (CBS)-chloroplast protein (CP12) fusion proteins. These consist of two domains, each recognized as stand-alone photosynthetic regulators with different functions described in cyanobacteria (CP12) and plants (CP12 and CBSX). Here we show that CBS-CP12 fusion proteins are encoded in distinct gene neighborhoods, several unrelated to photosynthesis. Most frequently, CBS-CP12 genes are in a gene cluster with thioredoxin A (TrxA), which is prevalent in bloom-forming, marine symbiotic, and benthic mat cyanobacteria. Focusing on a CBS-CP12 from Microcystis aeruginosa PCC 7806 encoded in a gene cluster with TrxA, we reveal that the domain fusion led to the formation of a hexameric protein. We show that the CP12 domain is essential for hexamerization and contains an ordered, previously structurally uncharacterized N-terminal region. We provide evidence that CBS-CP12, while combining properties of both regulatory domains, behaves different from CP12 and plant CBSX. It does not form a ternary complex with phosphoribulokinase (PRK) and glyceraldehyde-3-phosphate dehydrogenase. Instead, CBS-CP12 decreases the activity of PRK in an AMP-dependent manner. We propose that the novel domain architecture and oligomeric state of CBS-CP12 expand its regulatory function beyond those of CP12 in cyanobacteria. KW - crystal structure KW - hexamer KW - redox KW - Microcystis aeruginosa Y1 - 2018 U6 - https://doi.org/10.1073/pnas.1806668115 SN - 0027-8424 VL - 115 IS - 27 SP - 7141 EP - 7146 PB - National Acad. of Sciences CY - Washington ER -