Cbs-KO Mouse

Cbs, or cystathionine β -synthase, is an evolutionarily conserved protein domain present in the proteome of archaebacteria, prokaryotes, and eukaryotes [2]. CBS domains usually come in tandem repeats and are found in cytosolic and membrane proteins with various functions like metabolic enzymes, kinases, and channels [2]. They can form an intramolecular dimeric structure (CBS pair) [2]. Mutations in CBS domains of human proteins are associated with several hereditary diseases, such as homocystinuria, retinitis pigmentosa, hypertrophic cardiomyopathy, and myotonia congenital [2]. CBS domains are proposed to affect protein multimerization, sorting, channel gating, and ligand binding, and are hypothesized to function as sensors of intracellular metabolites [2].

CBS domains may undergo conformational changes upon binding of adenosine derivatives, metal ions, or nucleic acids [1]. The degree and direction of these changes depend on the ligand type, binding site features, and the association manner of Bateman modules (formed by paired CBS motifs) [1]. Regulatory CBS domains, existing as two or four tandem copies in numerous cytosolic and membrane-associated proteins, can act as auto-inhibitory regulatory units, and upon binding to adenosine nucleotides, they can either activate or further inhibit protein function, enabling proteins containing CBS domains to sense cell energy levels [3].

In summary, Cbs is a conserved protein domain with a crucial role in various cellular functions and protein regulation. Mutations in its domains are linked to multiple hereditary diseases. Understanding Cbs through studies on its structure-function relationships and ligand-binding properties can provide insights into the mechanisms underlying these diseases and potentially offer new strategies for diagnosis and treatment [1,2,3].

References:

1. Ereño-Orbea, June, Oyenarte, Iker, Martínez-Cruz, Luis Alfonso. 2013. CBS domains: Ligand binding sites and conformational variability. In Archives of biochemistry and biophysics, 540, 70-81. doi:10.1016/j.abb.2013.10.008. https://pubmed.ncbi.nlm.nih.gov/24161944/

2. Ignoul, Sofie, Eggermont, Jan. . CBS domains: structure, function, and pathology in human proteins. In American journal of physiology. Cell physiology, 289, C1369-78. doi:. https://pubmed.ncbi.nlm.nih.gov/16275737/

3. Baykov, Alexander A, Tuominen, Heidi K, Lahti, Reijo. 2011. The CBS domain: a protein module with an emerging prominent role in regulation. In ACS chemical biology, 6, 1156-63. doi:10.1021/cb200231c. https://pubmed.ncbi.nlm.nih.gov/21958115/