Solution structure and calcium-binding properties of EF-hands 3 and 4 of calsenilin.
Calsenilin is a member of the recoverin branch of the EF-hand superfamily that is reported to interact with presenilins, regulate prodynorphin gene expression, modulate voltage-gated Kv4 potassium channel function, and bind to neurotoxins. Calsenilin is a Ca+2-binding protein and plays an important role in calcium signaling. Despite its importance in numerous neurological functions, the structure of this protein has not been reported. In the absence of Ca+2, the protein has limited spectral resolution that increases upon the addition of Ca+2. Here, we describe the three-dimensional solution structure of EF-hands 3 and 4 of calsenilin in the Ca+2-bound form. The Ca+2-bound structure consists of five alpha-helices and one two-stranded antiparallel beta-sheet. The long loop that connects EF hands 3 and 4 is highly disordered in solution. In addition to its structural effects, Ca+2 binding also increases the protein's propensity to dimerize. These changes in structure and oligomerization state induced upon Ca+2 binding may play important roles in molecular recognition during calcium signaling.
Yu
Liping
L
Pharmaceutical Discovery Division, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6098, USA.
Sun
Chaohong
C
Mendoza
Renaldo
R
Wang
Jie
J
Matayoshi
Edmund D
ED
Hebert
Eric
E
Pereda-Lopez
Ana
A
Hajduk
Philip J
PJ
Olejniczak
Edward T
ET
D000595:Amino Acid Sequence; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D019281:Dimerization; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D051605:Kv Channel-Interacting Proteins; D015221:Potassium Channels; D002118:Calcium