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Protein & Peptide Letters
ISSN (Print): 0929-8665
ISSN (Online): 1875-5305
DOI: 10.2174/0929866511320050011      Price:  $58

Functional and Structural Analysis of the Conserved EFhd2 Protein

Author(s): Yancy Ferrer-Acosta, Eva N. Rodriguez Cruz, Ana del C. Vaquer and Irving E. Vega
Pages 573-583 (11)
EFhd2 is a novel protein conserved from C. elegans to H. sapiens. This novel protein was originally identified in cells of the immune and central nervous systems. However, it is most abundant in the central nervous system, where it has been found associated with pathological forms of the microtubule-associated protein tau. The physiological or pathological roles of EFhd2 are poorly understood. In this study, a functional and structural analysis was carried to characterize the molecular requirements for EFhd2’s calcium binding activity. The results showed that mutations of a conserved aspartate on either EF-hand motif disrupted the calcium binding activity, indicating that these motifs work in pair as a functional calcium binding domain. Furthermore, characterization of an identified single-nucleotide polymorphisms (SNP) that introduced a missense mutation indicates the importance of a conserved phenylalanine on EFhd2 calcium binding activity. Structural analysis revealed that EFhd2 is predominantly composed of alpha helix and random coil structures and that this novel protein is thermostable. EFhd2’s thermo stability depends on its N-terminus. In the absence of the N-terminus, calcium binding restored EFhd2’s thermal stability. Overall, these studies contribute to our understanding on EFhd2 functional and structural properties, and introduce it into the family of canonical EF-hand domain containing proteins.
EFHD2, calcium binding, EF-hand domain, coil-coiled domain, tau-associated protein, secondary structure
Department of Biology, University of Puerto Rico-Rio Piedras Campus, Julio García Diaz Bldg. #120, San Juan, PR 00931, USA.