Gitte A Jensen

Publications (2)8 Total impact

• Article: The C-terminal tail of human neuronal calcium sensor 1 regulates the conformational stability of the Ca²⁺₋ activated state.

  Pétur O Heidarsson, Ida J Bjerrum-Bohr, Gitte A Jensen, Olaf Pongs, Bryan E Finn, Flemming M Poulsen, Birthe B Kragelund
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  ABSTRACT: Neuronal calcium sensor 1 (NCS-1) and orthologs are expressed in all organisms from yeast to humans. In the latter, NCS-1 plays an important role in neurotransmitter release and interacts with a plethora of binding partners mostly through a large solvent-exposed hydrophobic crevice. The structural basis behind the multispecific binding profile is not understood. To begin to address this, we applied NMR spectroscopy to determine the solution structure of calcium-bound human NCS-1. The structure in solution demonstrates interdomain flexibility and, in the absence of a binding partner, the C-terminal tail residues occupy the hydrophobic crevice as a ligand mimic. A variant with a C-terminal tail deletion shows lack of a defined structure but maintained cooperative unfolding and dramatically reduced global stability. The results suggest that the C-terminal tail is important for regulating the conformational stability of the Ca(2+)-activated state. Furthermore, a single amino acid mutation that was recently diagnosed in a patient with autistic spectrum disorder was seen to affect the C-terminal tail and binding crevice in NCS-1.
  Journal of Molecular Biology 03/2012; 417(1-2):51-64. · 4.00 Impact Factor
• Source

  Available from: Birthe B. Kragelund

  Article: Binding site structure of one LRP-RAP complex: implications for a common ligand-receptor binding motif.

  Gitte A Jensen, Olav M Andersen, Alexandre M J J Bonvin, Ida Bjerrum-Bohr, Michael Etzerodt, Hans C Thøgersen, Charlotte O'Shea, Flemming M Poulsen, Birthe B Kragelund
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  ABSTRACT: The low-density lipoprotein receptor-related protein (LRP) interacts with more than 30 ligands of different sizes and structures that can all be replaced by the receptor-associated protein (RAP). The double module of complement type repeats, CR56, of LRP binds many ligands including all three domains of RAP and alpha2-macroglobulin, which promotes the catabolism of the Abeta-peptide implicated in Alzheimer's disease. To understand the receptor-ligand cross-talk, the NMR structure of CR56 has been solved and ligand binding experiments with RAP domain 1 (RAPd1) have been performed. From chemical shift perturbations of both binding partners upon complex formation, a HADDOCK model of the complex between CR56 and RAPd1 has been obtained. The binding residues are similar to a common binding motif suggested from alpha2-macroglobulin binding studies and provide evidence for an understanding of their mutual cross-competition pattern. The present structural results convey a simultaneous description of both binding partners of an LRP-ligand complex and open a route to a broader understanding of the binding specificity of the LRP receptor, which may involve a general four-residue receptor-ligand recognition motif common to all LRP ligands. The present result may be beneficial in the design of antagonists of ligand binding to the LDL receptor family, and especially of drugs for treatment of Alzheimer's disease.
  Journal of Molecular Biology 10/2006; 362(4):700-16. · 4.00 Impact Factor