Structural and functional insights into the unique CBS-CP12 fusion protein family in cyanobacteria

Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):7141-7146. doi: 10.1073/pnas.1806668115. Epub 2018 Jun 18.


Cyanobacteria are important photosynthetic organisms inhabiting a range of dynamic environments. This phylum is distinctive among photosynthetic organisms in containing genes encoding uncharacterized cystathionine β-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.

Keywords: Microcystis aeruginosa; crystal structure; hexamer; redox.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Chloroplast Proteins / genetics*
  • Chloroplast Proteins / metabolism
  • Cystathionine beta-Synthase / genetics*
  • Cystathionine beta-Synthase / metabolism
  • Microcystis / genetics*
  • Microcystis / metabolism
  • Multigene Family*
  • Protein Domains


  • Bacterial Proteins
  • Chloroplast Proteins
  • Cystathionine beta-Synthase

Associated data

  • PDB/5NMU
  • PDB/5NPL
  • PDB/5NVD