Peptides derived from human galectin-3 N-terminal tail interact with its carbohydrate recognition domain in a phosphorylation-dependent manner

详细信息    查看全文

• 作者：M. 脕lvaro Berb铆s ; Sabine Andr茅 ; F. Javier Ca帽ada ; R眉diger Pipkorn ; Hans Ippel ; Kevin H. Mayo ; Dieter K眉bler ; Hans-Joachim Gabius ; Jes煤s Jim茅nez-Barbero
• 关键词：CRD ; carbohydrate recognition domain ; Gal-3 ; galectin-3 ; HSQC ; heteronuclear single-quantum coherence ; NMR ; nuclear magnetic resonance
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：3 January, 2014
• 年：2014
• 卷：443
• 期：1
• 页码：126-131
• 全文大小：2390 K

文摘

Galectin-3 (Gal-3) is a multi-functional effector protein that functions in the cytoplasm and the nucleus, as well as extracellularly following non-classical secretion. Structurally, Gal-3 is unique among galectins with its carbohydrate recognition domain (CRD) attached to a rather long N-terminal tail composed mostly of collagen-like repeats (nine in the human protein) and terminating in a short non-collagenous terminal peptide sequence unique in this lectin family and not yet fully explored. Although several Ser and Tyr sites within the N-terminal tail can be phosphorylated, the physiological significance of this post-translational modification remains unclear. Here, we used a series of synthetic (phospho)peptides derived from the tail to assess phosphorylation-mediated interactions with ¹⁵N-labeled Gal-3 CRD. HSQC-derived chemical shift perturbations revealed selective interactions at the backface of the CRD that were attenuated by phosphorylation of Tyr 107 and Tyr 118, while phosphorylation of Ser 6 and Ser 12 was essential. Controls with sequence scrambling underscored inherent specificity. Our studies shed light on how phosphorylation of the N-terminal tail may impact on Gal-3 function and prompt further studies using phosphorylated full-length protein.