PDBsum entry 2kqy

Metal binding protein

PDB id: 2kqy

Contents

Protein chain

108 a.a. *

* Residue conservation analysis

PDB id:

2kqy

Name:

Metal binding protein

Title:

Solution structure of avian thymic hormone

Structure:

Parvalbumin, thymic. Chain: a. Synonym: avian thymic hormone, ath, thymus-specific antigen t1. Engineered: yes

Source:

Gallus gallus. Chicken. Organism_taxid: 9031. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: de3.

NMR struc:

20 models

Authors:

M.T.Henzl

Key ref:

J.P.Schuermann et al. (2010). Structure of avian thymic hormone, a high-affinity avian beta-parvalbumin, in the Ca2+-free and Ca2+-bound states. J Mol Biol, 397, 991-1002. PubMed id: 20156445

Date:

24-Nov-09 Release date: 07-Apr-10

Protein chain

P19753  (PRVT_CHICK) -  Parvalbumin, thymic from Gallus gallus

Seq: 109 a.a.

Struc: 108 a.a.

J Mol Biol 397:991-1002 (2010)

PubMed id: 20156445

Structure of avian thymic hormone, a high-affinity avian beta-parvalbumin, in the Ca2+-free and Ca2+-bound states.

J.P.Schuermann, A.Tan, J.J.Tanner, M.T.Henzl.

ABSTRACT

Originally isolated on the basis of its capacity to stimulate T-cell maturation and proliferation, avian thymic hormone (ATH) is nevertheless a parvalbumin, one of two beta-lineage isoforms expressed in birds. We recently learned that addition of Ca(2+)-free ATH to a solution of 8-anilinonaphthalene-1-sulfonate (ANS) markedly increases ANS emission. This behavior, not observed in the presence of Ca(2+), suggests that apolar surface area buried in the Ca(2+)-bound state becomes solvent accessible upon Ca(2+) removal. In order to elucidate the conformational alterations that accompany Ca(2+) binding, we have obtained the solution structure of the Ca(2+)-free protein using NMR spectroscopy and compared it to the Ca(2+)-loaded protein, solved by X-ray crystallography. Although the metal-ion-binding (CD-EF) domains are largely coincident in the superimposed structures, a major difference is observed in the AB domains. The tight association of helix B with the E and F helices in the Ca(2+)-bound state is lost upon removal of Ca(2+), producing a deep hydrophobic cavity. The B helix also undergoes substantial rotation, exposing the side chains of F24, Y26, F29, and F30 to solvent. Presumably, the increase in ANS emission observed in the presence of unliganded ATH reflects the interaction of these hydrophobic residues with the fluorescent probe. The increased solvent exposure of apolar surface area in the Ca(2+)-free protein is consistent with previously collected scanning calorimetry data, which indicated an unusually low change in heat capacity upon thermal denaturation. The Ca(2+)-free structure also provides added insight into the magnitude of ligation-linked conformational alteration compatible with a high-affinity metal-ion-binding signature. The exposure of substantial apolar surface area suggests the intriguing possibility that ATH could function as a reverse Ca(2+) sensor.