期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms7937
关键词
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资金
- ARAID
- MEC [BFU2010-19504, CTQ2013-44367-C2-2-P, CTQ2011-25871, BIO2010-14983, CTQ2012-36365, MAT2012-38318]
- DNRF [DNRF107]
- DGA [B89, B18]
- Generalitat de Catalunya [2014SGR-987]
- ANR-CHEX
- ATIP-Avenir
- FP7 under BioStruct-X [283570, BIOSTRUCTX_5186]
- ICREA Funding Source: Custom
Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity and relies on a flexible linker located between the catalytic and the lectin domains. Our results also shed light on how GalNAc-Ts generate dense decoration of proteins with O-glycans.
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