skip to main content

SciTech ConnectSciTech Connect

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

Highlights: •Galectin-3 is composed of a carbohydrate recognition domain and an N-terminal tail. •Synthetic peptides derived from the tail are shown to interact with the CRD. •This interaction is modulated by Ser- and Tyr-phosphorylation of the peptides. -- Abstract: 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 {sup 15}N-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 phosphorylationmore » of the N-terminal tail may impact on Gal-3 function and prompt further studies using phosphorylated full-length protein.« less
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [5] ;  [6] ;  [7] ;  [2] ;  [1]
  1. Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid (Spain)
  2. Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University, 80539 Munich (Germany)
  3. Central Peptide Synthesis Unit, German Cancer Research Center, 69120 Heidelberg (Germany)
  4. Department of Biochemistry, CARIM, University of Maastricht, Maastricht (Netherlands)
  5. (United States)
  6. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455 (United States)
  7. Biomolecular Interactions, German Cancer Research Center, 69120 Heidelberg (Germany)
Publication Date:
OSTI Identifier:
22242239
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 443; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AGGLUTININS; AMINO ACID SEQUENCE; CARBOHYDRATES; CHEMICAL SHIFT; COLLAGEN; CYTOPLASM; INTERACTIONS; NUCLEAR MAGNETIC RESONANCE; PEPTIDES; PHOSPHORYLATION