Structure of rat parvalbumlin with deleted AB domain: Implications for theevolution of EF hand calcium-binding proteins and possible physiological relevance

Citation
M. Thepaut et al., Structure of rat parvalbumlin with deleted AB domain: Implications for theevolution of EF hand calcium-binding proteins and possible physiological relevance, PROTEINS, 45(2), 2001, pp. 117-128
Citations number
56
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEINS-STRUCTURE FUNCTION AND GENETICS
ISSN journal
0887-3585 → ACNP
Volume
45
Issue
2
Year of publication
2001
Pages
117 - 128
Database
ISI
SICI code
0887-3585(20011101)45:2<117:SORPWD>2.0.ZU;2-O
Abstract
Among the EF-hand Ca2+-binding proteins, parvalbumin (PV) and calbindin D9k (CaB) have the function of Ca2+ buffers. They evolved from an ancestor pro tein through two phylogenetic pathways, keeping one pair of EF-hands. They differ by the extra helix-loop-helix (AB domain) found in PV and by the lin ker between the binding sites. To investigate whether the deletion of AB in PV restores a CaB-like structure, we prepared and solved the structure of the truncated rat PV (PVrat Delta 37) by X-ray and NMR. PVrat Delta 37 keep s the PV fold, but is more compact, having a well-structured linker, which differs remarkably from CaB. Pvrat Delta 37 has no stable apo-form, has low er affinity for Ca2+ than full-length PV, and does not bind Mg2+, in contra st to CaB. Structural differences of the hydrophobic core are partially res ponsible for lowering the calcium-binding affinity of the truncated protein . It can be concluded that the AB domain, like the linker of CaB, plays a r ole in structural stabilization. The AB domain of PV protects the hydrophob ic core, and is required to maintain high affinity for divalent cation bind ing. Therefore, the AB domain possibly modulates PV buffer function. (C) 20 01 Wiley-Liss, Inc.