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Authors: Malzbender, Kristina Lois
Advisors: Ando, Nozomi
Department: Chemistry
Class Year: 2015
Abstract: Human galectin-4 (hGal4) is a member of the galectin family of proteins with a variety of cellular functions including cell cycle regulation, immunological functions and cell migration. hGal4 is found in the human alimentary tract and has also been implicated in a variety of cancers and inflammatory bowel disease. For this reason, hGal4 has been proposed as a potential drug target or marker for cancer diagnoses. However structural information of the full-length protein is lacking. hGal4 belongs to the tandem-repeat type subfamily of galectins, characterized by two distinct carbohydrate recognition domains within a single peptide chain. The two domains have a conserved amino acid signature shared by all galectins and are linked by a flexible peptide chain. This flexibility has rendered hGal4 difficult to study by traditional structural methods. In the current study, I investigate the structural dynamics of hGal4 using small angle x-ray scattering (SAXS). Using both oscillating-flow cell SAXS and in-line size exclusion chromatography SAXS, I investigated the conformational changes of hGal4 in solution as a function of lactose. This data allowed us to determine the radius of gyration (R\(_{g}\)) and maximum interparticle distance (D\(_{max}\)). Furthermore, the SAXS data collected were used to generate ab-initio shape reconstructions for hGal4 both with and without lactose using dummy residue modeling and rigid-body ensemble modeling. My results demonstrate that the flexible peptide linker between the two carbohydrate recognition domains of hGal4 confers conformational flexibility that allows the protein to bind to carbohydrate ligands in an extended conformation and bring together the two domains into a compact structure.
Extent: 78 pages
Type of Material: Princeton University Senior Theses
Language: en_US
Appears in Collections:Chemistry, 1926-2017

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