Journal Article

PUBDB-2015-01344

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The C-Terminal Random Coil Region Tunes the $\mathrm{Ca^{2+}}$-Binding Affinity of S100A4 through Conformational Activation

Csernoch, L. (Corresponding Author) ; Kiss, B. ; Lundholm, I.>Extern* ; Bodor, A. ; Petoukhov, M. V. ; Svergun, D. I. ; Nyitray, L. ; Katona, G.>Extern* ; Csernoch, L.

2014
PLoS Lawrence, Kan.

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Please use a persistent id in citations: doi:10.1371/journal.pone.0097654

Abstract: S100A4 interacts with many binding partners upon Ca2+ activation and is strongly associated with increased metastasis formation. In order to understand the role of the C-terminal random coil for the protein function we examined how small angle X-ray scattering of the wild-type S100A4 and its C-terminal deletion mutant (residues 1–88, Δ13) changes upon Ca2+ binding. We found that the scattering intensity of wild-type S100A4 changes substantially in the 0.15–0.25 Å−1 q-range whereas a similar change is not visible in the C-terminus deleted mutant. Ensemble optimization SAXS modeling indicates that the entire C-terminus is extended when Ca2+ is bound. Pulsed field gradient NMR measurements provide further support as the hydrodynamic radius in the wild-type protein increases upon Ca2+ binding while the radius of Δ13 mutant does not change. Molecular dynamics simulations provide a rational explanation of the structural transition: the positively charged C-terminal residues associate with the negatively charged residues of the Ca2+-free EF-hands and these interactions loosen up considerably upon Ca2+-binding. As a consequence the Δ13 mutant has increased Ca2+ affinity and is constantly loaded at Ca2+ concentration ranges typically present in cells. The activation of the entire C-terminal random coil may play a role in mediating interaction with selected partner proteins of S100A4.

Note: OA

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. DORIS Beamline X1 (POF2-54G13) (POF2-54G13)

Experiment(s):

1. DORIS Beamline X1 (DORIS III)

Appears in the scientific report 2014

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Database coverage:
; ; ; ; BIOSIS Previews ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record

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