TY - JOUR
T1 - Full-length model of the human galectin-4 and insights into dynamics of inter-domain communication
AU - Rustiguel, Joane K.
AU - Soares, Ricardo O.S.
AU - Meisburger, Steve P.
AU - Davis, Katherine M.
AU - Malzbender, Kristina L.
AU - Ando, Nozomi
AU - Dias-Baruffi, Marcelo
AU - Nonato, Maria Cristina
PY - 2016/9/19
Y1 - 2016/9/19
N2 - Galectins are proteins involved in diverse cellular contexts due to their capacity to decipher and respond to the information encoded by β-galactoside sugars. In particular, human galectin-4, normally expressed in the healthy gastrointestinal tract, displays differential expression in cancerous tissues and is considered a potential drug target for liver and lung cancer. Galectin-4 is a tandem-repeat galectin characterized by two carbohydrate recognition domains connected by a linker-peptide. Despite their relevance to cell function and pathogenesis, structural characterization of full-length tandem-repeat galectins has remained elusive. Here, we investigate galectin-4 using X-ray crystallography, small-and wide-Angle X-ray scattering, molecular modelling, molecular dynamics simulations, and differential scanning fluorimetry assays and describe for the first time a structural model for human galectin-4. Our results provide insight into the structural role of the linker-peptide and shed light on the dynamic characteristics of the mechanism of carbohydrate recognition among tandem-repeat galectins.
AB - Galectins are proteins involved in diverse cellular contexts due to their capacity to decipher and respond to the information encoded by β-galactoside sugars. In particular, human galectin-4, normally expressed in the healthy gastrointestinal tract, displays differential expression in cancerous tissues and is considered a potential drug target for liver and lung cancer. Galectin-4 is a tandem-repeat galectin characterized by two carbohydrate recognition domains connected by a linker-peptide. Despite their relevance to cell function and pathogenesis, structural characterization of full-length tandem-repeat galectins has remained elusive. Here, we investigate galectin-4 using X-ray crystallography, small-and wide-Angle X-ray scattering, molecular modelling, molecular dynamics simulations, and differential scanning fluorimetry assays and describe for the first time a structural model for human galectin-4. Our results provide insight into the structural role of the linker-peptide and shed light on the dynamic characteristics of the mechanism of carbohydrate recognition among tandem-repeat galectins.
UR - https://www.scopus.com/pages/publications/84988431038
UR - https://www.scopus.com/pages/publications/84988431038#tab=citedBy
U2 - 10.1038/srep33633
DO - 10.1038/srep33633
M3 - Article
C2 - 27642006
AN - SCOPUS:84988431038
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 33633
ER -