TitleOrder and disorder in proteins
NameErtekin, Asli (author), Montelione, Gaetano T (chair), Nanda, Vikas (internal member), Baum, Jean (internal member), Stock, Ann M (internal member), Anderson, Stephen (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectComputational Biology and Molecular Biophysics,
DescriptionIn contrast to the general view that proteins should have a specific 3D structure in solution for their activity, there are many proteins which do not have a folded “native” structure for a big portion of their sequence. While these intrinsically disordered regions are essential for protein function, they cause problems in efforts for determining the 3D structures for the folded domains. It has been shown that the removal of the disordered domains improved the structure determination success both by X-ray crystallography and by NMR. As part of Northeast Structural Genomics (NESG) effort I worked on identifying the disordered and flexible parts of the protein using Hydrogen/Deuterium Exchange with Mass Spectroscopy (HDX-MS) analysis for construct optimization for high-throughput structure determination. Using this method I also studied human Smad3, which is an important part of the TGF-β-signaling pathway; and provided the first experimental data on structural features of the linker domain. During my training, I also studied human Deleted in Oral Cancer (DOC-1) protein, which was one of the proteins I studied by HDX-MS for construct optimization. We determined the solution structure of the folded region of DOC-1, which was shown to be important in cell-cycle regulation and cancer biology; and I also studied structure-function relations. Additionally, we studied the solution structure of Methionine Sulfoxide Reductase B from Bacillus subtilis, an important protein for reversing oxidative damage in cells, by NMR as a part of methods development studies for NMR for large proteins.
NoteIncludes bibliographical references
Noteby Asli Ertekin
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.