Ca-Dependent Folding of Human Calumenin

• Published in: PloS one Vol. 11; no. 3; p. e0151547
• Main Authors: Mazzorana, Marco, Hussain, Rohanah, Sorensen, Thomas
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.03.2016; Public Library of Science (PLoS)
• Subjects: Amino Acid Sequence; Binding; Binding proteins; Biology and Life Sciences; Ca2+-transporting ATPase; Calcium; Calcium - chemistry; Calcium ions; Calcium-Binding Proteins - metabolism; Circular Dichroism; Cloning, Molecular; Dichroism; EF-hand; EF-hand protein; Endoplasmic reticulum; Escherichia coli - genetics; Escherichia coli - metabolism; Hand protein; Homeostasis; Humans; Life sciences; Medicine and Health Sciences; Molecular structure; Physical Sciences; Physiological aspects; Protein Binding; Protein folding; Protein Folding - drug effects; Protein structure; Protein Structure, Tertiary - physiology; Proteins; Research and Analysis Methods; Scattering, Small Angle; Secondary structure; Smooth muscle; Structure; Surface Plasmon Resonance; Switches; X-Ray Diffraction; Zebrafish; United Kingdom; United Kingdom > UK
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0151547

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.