title: Ca-Dependent Folding of Human Calumenin.
abstract: Human calumenin (hCALU) is a six EF-hand protein belonging to the CREC family. As other members of the family, it is localized in the secretory pathway and regulates the activity of SERCA2a and of the ryanodine receptor in the endoplasmic reticulum (ER). We have studied the effects of Ca2+ binding to the protein and found it to attain a more compact structure upon ion binding. Circular Dichroism (CD) measurements suggest a major rearrangement of the protein secondary structure, which reversibly switches from disordered at low Ca2+ concentrations to predominantly alpha-helical when Ca2+ is added. SAXS experiments confirm the transition from an unfolded to a compact structure, which matches the structural prediction of a trilobal fold. Overall our experiments suggest that calumenin is a Ca2+ sensor, which folds into a compact structure, capable of interacting with its molecular partners, when Ca2+ concentration within the ER reaches the millimolar range.
authors.affiliation: Diamond Light Source, Ltd, Life Sciences Division, Harwell Science and Innovation Campus, Didcot, United Kingdom.
authors.forename: Marco
authors.initials: M
authors.lastname: Mazzorana
authors.affiliation: Diamond Light Source, Ltd, Life Sciences Division, Harwell Science and Innovation Campus, Didcot, United Kingdom.
authors.forename: Rohanah
authors.initials: R
authors.lastname: Hussain
authors.affiliation: Diamond Light Source, Ltd, Life Sciences Division, Harwell Science and Innovation Campus, Didcot, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sorensen
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000737:chemistry*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002942:Circular Dichroism; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D017510:Protein Folding / Q000187:drug effects*; D017434:Protein Structure, Tertiary / Q000502:physiology; D053838:Scattering, Small Angle; D020349:Surface Plasmon Resonance; D014961:X-Ray Diffraction
chemical_list: C510527:CALU protein, human; D002135:Calcium-Binding Proteins; D002118:Calcium