4WMO

Selenomethionine derivative of Xenopus laevis embryonic epidermal lectin carbohydrate-binding domain

Summary for 4WMO

• Entry DOI: 10.2210/pdb4wmo/pdb
• Related: 4WN0
• Descriptor: XEEL protein, CALCIUM ION, PENTAETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: lectin, carbohydrate-binding protein, calcium, trimer, fibrinogen-like domain, x-type lectin, innate immunity, sugar binding protein
• Biological source: Xenopus laevis (African clawed frog)
• Cellular location: Secreted : Q5PPM0
• Total number of polymer chains: 6
• Total formula weight: 195945.04

Authors

Wangkanont, K.,Kiessling, L.L.,Forest, K.T. (deposition date: 2014-10-09, release date: 2016-01-20, Last modification date: 2023-12-27)

Primary citation

Wangkanont, K.,Wesener, D.A.,Vidani, J.A.,Kiessling, L.L.,Forest, K.T.
Structures of Xenopus Embryonic Epidermal Lectin Reveal a Conserved Mechanism of Microbial Glycan Recognition.
J.Biol.Chem., 291:5596-5610, 2016

PubMed Abstract: Intelectins (X-type lectins), broadly distributed throughout chordates, have been implicated in innate immunity. Xenopus laevis embryonic epidermal lectin (XEEL), an intelectin secreted into environmental water by the X. laevis embryo, is postulated to function as a defense against microbes. XEEL is homologous (64% identical) to human intelectin-1 (hIntL-1), which is also implicated in innate immune defense. We showed previously that hIntL-1 binds microbial glycans bearing exocyclic vicinal diol groups. It is unknown whether XEEL has the same ligand specificity. Also unclear is whether XEEL and hIntL-1 have similar quaternary structures, as XEEL lacks the corresponding cysteine residues in hIntL-1 that stabilize the disulfide-linked trimer. These observations prompted us to further characterize XEEL. We found that hIntL-1 and XEEL have similar structural features. Even without the corresponding intermolecular disulfide bonds present in hIntL-1, the carbohydrate recognition domain of XEEL (XEELCRD) forms a stable trimer in solution. The structure of XEELCRD in complex with d-glycerol-1-phosphate, a residue present in microbe-specific glycans, indicated that the exocyclic vicinal diol coordinates to a protein-bound calcium ion. This ligand-binding mode is conserved between XEEL and hIntL-1. The domain architecture of full-length XEEL is reminiscent of a barbell, with two sets of three glycan-binding sites oriented in opposite directions. This orientation is consistent with our observation that XEEL can promote the agglutination of specific serotypes of Streptococcus pneumoniae. These data support a role for XEEL in innate immunity, and they highlight structural and functional conservation of X-type lectins among chordates.

PubMed: 26755729
DOI: 10.1074/jbc.M115.709212

Experimental method

X-RAY DIFFRACTION (2.3 Å)