Open AccessFunctional and Structural Analysis of the Conserved EFhd2 Protein
Author(s) -
Yancy Ferrer-Acosta,
Eva N. Rodriguez Cruz,
Ana del C. Vaquer,
Irving E. Vega
Publication year - 2013
Publication title -
protein and peptide letters/protein and peptide letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 58
eISSN - 1875-5305
pISSN - 0929-8665
DOI - 10.2174/0929866511320050011
Subject(s) - calcium binding protein , biology , conserved sequence , structural motif , missense mutation , mutation , genetics , biochemistry , peptide sequence , calcium , chemistry , gene , organic chemistry
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.