The structure of DC-SIGNR with a portion of its repeat domain lends insights to modeling of the receptor tetramer

JOURNAL OF MOLECULAR BIOLOGY

卷:347

Article

Snyder, GA ; Colonna, M ; Sun, PD

关键词: DC-SIGN;    HIV gp120;    C-type lectin;    dendritic cell;    X-ray structure;   

DOI  :  10.1016/j.jmb.2005.01.063

来源: Elsevier

【 摘 要 】

The dendritic cell-specific ICAM-3 non-integrin (DC-SIGN) and its close relative DC-SIGNR recognize various glycoproteins, both pathogenic and of cellular, through the receptor lectin domain-mediated carbohydrate recognition. While the carbohydrate-recognition domains (CRD) exist as monomers and bind individual carbohydrates with low affinity and are permissive in nature, the full-length receptors form tetramers through their repeat domain and recognize specific ligands with high affinity. To understand the tetramer-based ligand binding avidity, we determined the crystal structure of DC-SIGNR with its last repeat region. Compared to the carbohydrate-bound CRD structure, the structure revealed conformational changes in the calcium and carbohydrate coordination loops of CRD, an additional disulfide bond between the N and the C termini of the CRD, and a helical conformation for the last repeat. On the basis of the current crystal structure and other published structures with sequence homology to the repeat domain, we generated a tetramer model for DC-SlGN/R using homology modeling and propose a ligand-recognition index to identify potential receptor ligands. Published by Elsevier Ltd.

【 授权许可】

Free