title: Full-length model of the human galectin-4 and insights into dynamics of inter-domain communication.
abstract: 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.
authors.affiliation: Laboratório de Cristalografia de Proteínas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, SP, Brazil.
authors.forename: Joane K
authors.initials: JK
authors.lastname: Rustiguel
authors.affiliation: Laboratório de Cristalografia de Proteínas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, SP, Brazil.
authors.forename: Ricardo O S
authors.initials: RO
authors.lastname: Soares
authors.affiliation: Department of Chemistry, Princeton University, Princeton, NJ, USA.
authors.forename: Steve P
authors.initials: SP
authors.lastname: Meisburger
authors.affiliation: Department of Chemistry, Princeton University, Princeton, NJ, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Davis
authors.affiliation: Department of Chemistry, Princeton University, Princeton, NJ, USA.
authors.forename: Kristina L
authors.initials: KL
authors.lastname: Malzbender
authors.affiliation: Department of Chemistry, Princeton University, Princeton, NJ, USA.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Ando
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, SP, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Dias-Baruffi
authors.affiliation: Laboratório de Cristalografia de Proteínas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, SP, Brazil.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Nonato
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D037541:Galectin 4 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D012995:Solubility; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D037541:Galectin 4