| 1.C.96 The Haemolytic Lectin, CEL-III (CEL-III) Family
CEL-III is an oligomeric haemolytic lectin, which has two beta-trefoil domains
(domains 1 and 2) and a beta-sheet-rich domain (domain 3). In domain 3
(residues 284-432), there is a hydrophobic region containing two
alpha-helices (H8 and H9, residues 317-357) and a loop between them, in
which alternate hydrophobic residues, especially Val residues, are
present. To elucidate the role of the alpha-helix region in the
haemolytic process, peptides corresponding to different parts of this
region were synthesized and characterized (Hisamatsu et al., 2008). The peptides containing the
sequence that corresponded to the loop and second alpha-helix (H9)
showed the strongest antibacterial activity for Staphylococcus aureus and Bacillus subtilis through a marked permeabilization of the
bacterial cell membrane. Replacement of Lys405 in domain 3 of CEL-III by smaller residues led to a marked increase in hemolytic activity,
suggesting that moderately destabilizing domain 3 facilitates formation of transmembrane pores
through conformational changes (Nagao et al. 2016).
CEL-III is a Ca2+-dependent, galactose-specific lectin
from the sea cucumber, Cucumaria echinata, which exhibits hemolytic and
hemagglutinating activities. Six molecules of CEL-III
oligomerize to form an ion-permeable pore in the cell membrane (Uchida et al. 2004). The crystal structure of CELIII at 1.7 A resolution revealed three distinct domains: two N-terminal
two carbohydrate-binding domains (1 and 2), which adopt beta-trefoil
folds such as the B-chain of ricin and are members of the (QXW)(3) motif
family; and domain 3, which has a fold composed of two
alpha-helices and one beta-sandwich. CEL-III binds five Ca2+ ions at five of the six subdomains in both domains 1 and 2. These domains may rearrange upon carbohydrate binding in the erythrocyte
membrane and be responsible for
oligomerization and hemolysis (Uchida et al. 2004).
The generalized transport reaction catalyzed by CEL-III is:
Molecules (in) →  Molecules (out)
|
| References: |
Hisamatsu, K., N. Tsuda, S. Goda, and T. Hatakeyama. (2008). Characterization of the {alpha}-helix region in domain 3 of the haemolytic lectin CEL-III: implications for self-oligomerization and haemolytic processes. J Biochem 143: 79-86.
|
Nagao, T., R. Masaki, H. Unno, S. Goda, and T. Hatakeyama. (2016). Effects of amino acid mutations in the pore-forming domain of the hemolytic lectin CEL-III. Biosci. Biotechnol. Biochem. 1-4. [Epub: Ahead of Print]
|
Uchida, T., T. Yamasaki, S. Eto, H. Sugawara, G. Kurisu, A. Nakagawa, M. Kusunoki, and T. Hatakeyama. (2004). Crystal structure of the hemolytic lectin CEL-III isolated from the marine invertebrate Cucumaria echinata: implications of domain structure for its membrane pore-formation mechanism. J. Biol. Chem. 279: 37133-37141.
|
Unno H., Goda S. and Hatakeyama T. (2014). Hemolytic lectin CEL-III heptamerizes via a large structural transition from alpha-helices to a beta-barrel during the transmembrane pore formation process. J Biol Chem. 289(18):12805-12.
|
| Examples: |
| TC# | Name | Organismal Type | Example |
| 1.C.96.1.1 | The haemolytic lectin, CEL-III (Uchida et al. 2004). CEL-III heptamerizes via a large structural transition from alpha-helices to a
beta-barrel during the transmembrane pore-formation process (Unno et al. 2014). | Echinoderms | CEL-III of Cucumaria echinata (Q868M7) |
| |
| 1.C.96.1.2 | Putative pore-forming lectin toxin of 481 aas. | Animals | Putative toxin of Acropora millepora (Staghorn coral)
|
| |
| 1.C.96.1.3 | Putative uncharacterized α-1,2-mannosidase of 608 aas | | UP of Streptomyces rubidus |
| |
| 1.C.96.1.4 | Uncharacterized protein of 278 aas | | UP of Delftia tsuruhatensis |
| |
| Examples: |
| TC# | Name | Organismal Type | Example |
| 1.C.96.2.1 | Uncharacterized protein of 514 aas | Proteobacteria | UP of Moritella sp. PE36 |
| |
| 1.C.96.2.2 | Uncharacterized protein of 255 aas and 0 TMSs | | UP of Photorhabdus temperata |
| |
| 1.C.96.2.3 | Uncharacterized protein of 249 aa | | UP of Brevibacillus laterosporus |
| |
| 1.C.96.2.4 | Uncharacterized protein of 271 aas | | UP of Polaromonas glacialis |
| |
| Examples: |
| TC# | Name | Organismal Type | Example |
| 1.C.96.3.1 | Uncharacterized protein of 376 aas | | UP of Streptomyces griseofuscus |
| |
| 1.C.96.3.2 | Uncharacterized protein of 413 aas | | UP of Murinocardiopsis flavida |
| |
| 1.C.96.3.3 | Uncharacterized protein of 373 aas | | UP of Nocardiopsis sp. |
| |