Structure, binding interface and hydrophobic transitions of Ca 2+-loaded calbindin-D28K

Douglas J. Kojetin, Ronald A. Venters, David R. Kordys, Richele J. Thompson, Rajiv Kumar, John Cavanagh

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Calbindin-D28K is a Ca2+-binding protein, performing roles as both a calcium buffer and calcium sensor. The NMR solution structure of Ca2+-loaded calbindin-D28K reveals a single, globular fold consisting of six distinct EF-hand subdomains, which coordinate Ca 2+ in loops on EF1, EF3, EF4 and EF5. Target peptides from Ran-binding protein M and myo-inositol monophosphatase, along with a new target from procaspase-3, are shown to interact with the protein on a surface comprised of α5 (EF3), α8 (EF4) and the EF2-EF3 and EF4-EF5 loops. Fluorescence experiments reveal that calbindin-D28K adopts discrete hydrophobic states as it binds Ca2+. The structure, binding interface and hydrophobic characteristics of Ca2+-loaded calbindin-D 28K provide the first detailed insights into how this essential protein may function. This structure is one of the largest high-resolution NMR structures and the largest monomeric EF-hand protein to be solved to date.

Original languageEnglish (US)
Pages (from-to)641-647
Number of pages7
JournalNature Structural and Molecular Biology
Volume13
Issue number7
DOIs
StatePublished - Jul 2006

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Calbindin 1
EF Hand Motifs
Calcium
Calbindins
Proteins
Caspase 3
Carrier Proteins
Buffers
Fluorescence
Peptides

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Structure, binding interface and hydrophobic transitions of Ca 2+-loaded calbindin-D28K. / Kojetin, Douglas J.; Venters, Ronald A.; Kordys, David R.; Thompson, Richele J.; Kumar, Rajiv; Cavanagh, John.

In: Nature Structural and Molecular Biology, Vol. 13, No. 7, 07.2006, p. 641-647.

Research output: Contribution to journalArticle

Kojetin, Douglas J. ; Venters, Ronald A. ; Kordys, David R. ; Thompson, Richele J. ; Kumar, Rajiv ; Cavanagh, John. / Structure, binding interface and hydrophobic transitions of Ca 2+-loaded calbindin-D28K. In: Nature Structural and Molecular Biology. 2006 ; Vol. 13, No. 7. pp. 641-647.
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