The CFEM domain is a fungal-specific domain that contains eight cysteines and is found in some proteins with proposed roles in fungal pathogenesis [ PUBMED:12633989 ].

The structure of the CFEM domain containing protein 'Surface antigen protein 2' from Candida albicans ( Q5A0X8 … expand

The CFEM domain is a fungal-specific domain that contains eight cysteines and is found in some proteins with proposed roles in fungal pathogenesis [ PUBMED:12633989 ].

The structure of the CFEM domain containing protein 'Surface antigen protein 2' from Candida albicans ( Q5A0X8 ) has been solved [ PUBMED:27617569 ].

The CFEM (Common in Fungal Extracellular Membrane) protein domain is unique to fungi, but it is not found in all fungi. Many CFEM domain proteins have been found exclusively from Ascomycota and Basidiomycota, and they were found to be enriched in pathogenic fungi. The CFEM domain is found primarily in glycosylphosphatidylinositol (GPI)-anchored cell-wall proteins, and present in one or more copies, normally with one copy near the N terminus of proteins. CFEM-containing proteins are involved in differentiation, stress response and pathogenicity. CFEM-containing proteins systematically contribute to iron acquisition during saprotrophic and pathogenic growth in filamentous mycopathogens as well as inter-species competition. CFEM proteins have been shown to bind haem and to play crucial roles in extracting it from the host haemoglobin, as well as in mediating its delivery to the fungal cel [ PUBMED:12633989 PUBMED:27617569 PUBMED:34682292 PUBMED:35523457 ].

The CFEM domain is predominantly comprised of hybrophobic residues. CFEM domains contain eight characteristically spaced cysteine residues with the consensus sequence P-x-C-[AG]-x(2)-C-x(8,12)-C-x(1,4)-D-x(2,5)-C-x-C-x(9,14)-C-x(3,4)-C-x(15,16) (where x is any residue with its range shown). The CFEM domain adopts a helical-basket fold that consists of six α-helices, the third of which is perpendicular to a central bundle of five antiparallel helices. Overall, the shape of the helical portion resembles a basket that is 'capped' from the top by Helix 3, whereas the long N-terminalloop appears as its 'handle'.

The uniqueness of the helical-basket fold appears to stem primarily from the formation of four distinctive disulfide bonds that probably contribute to its rigidity and compactness, as well as to the distinctive orientation between its helices. These S-S bridges are formed between the eight canonical cysteine residues of the CFEM domain.Topologically, helices 2 and 4 are held together via two disulfide bridges, one formed by the first and the seventh cysteine residues (C1-C7) and the second by the second and sixth (C2-C6). Helices 3 and 5 are linked via a single disulfide bond (C5-C8), and Helix 3 is linked to an important haem-interacting loop via the C3-C4 disulfide bridge. The planar haem molecule is bound between a flat hydrophobic platform located on top of the helical basket and a peripheral N-terminal 'handle' extension. Exceptionally, an aspartic residue serves as the CFEM axial ligand, and so confers coordination of Fe(3) haem, but not of Fe(2) [ PUBMED:12633989 PUBMED:27617569 ].