Calcium-Binding Proteins and Their Role in Allergic Diseases Nicole Wopfner, PhD a, * , Oliver Dissertori, BSc b , Fatima Ferreira, PhD a , Peter Lackner, PhD b, * a Department of Molecular Biology, Christian Doppler Laboratory for Allergy Diagnostic and Therapy, University of Salzburg, Hellbrunnerstrasse 34, A-5020 Salzburg, Austria b Department of Molecular Biology, Division of Genomics, University of Salzburg, Hellbrunnerstrasse 34, A-5020 Salzburg, Austria Extensive cross-reactivity within allergenic plants likely is caused by three families of widely distributed panallergens: the profilins, the calcium-bind- ing proteins (CBPs), and the nonspecific lipid transfer proteins. Various CBPs have been isolated from pollen (grasses, trees, and weeds), parasites, fish, and man and were described as highly cross-reactive allergens not just in pollen but also in food [1]. CBPs exhibit a great diversity of composition, structure, Ca 2þ -binding, and target interaction properties [2]. These proteins may act simply as cal- cium carrier and buffer, ordbecause of calcium-induced changesdinteract with proteins in a calcium-dependent manner, and, thus, act as cellular messengers [3]. In general, calcium-binding proteins can be classified into 32 distinct subfamilies of proteins that may contain from two to eight calcium-binding domains called EF-hands (helix-loop-helix motifs). The EF-hand superfamily of proteins includes proteins like calmodulin, troponin C, myosin light chain, and more than 100 others. The canonical EF-hand is a highly conserved portion of these proteins and consists of an alpha helix, a loop around the bound calcium ion, and a second alpha helix (Fig. 1). Calcium ions usually bind to the EF-hand domain through four carboxylate or carboxyamide groups and one single backbone carbonyl oxygen placed in the loop with a specific spacing [4]. There are more than 3000 EF- hand–related entries in the National Center for Biotechnology Information This work was supported by Project S-8802 from the Austrian Research Council (FWF). * Corresponding author. E-mail addresses: nicole.wopfner@sbg.ac.at (N. Wopfner); peter.lackner@sbg.ac.at (P. Lackner). 0889-8561/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.iac.2006.10.003 immunology.theclinics.com Immunol Allergy Clin N Am 27 (2007) 29–44