4CFQ

Ca-bound truncated (delta13C) and C3S, C81S and C86S mutated S100A4 complexed with non-muscle myosin IIA

Summary for 4CFQ

• Entry DOI: 10.2210/pdb4cfq/pdb
• Related: 4CFR
• Descriptor: PROTEIN S100-A4, MYOSIN-9, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: ca-binding protein-motor protein complex, s100a4 proteins, ef-hand, ca-binding protein/motor protein
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 6
• Total formula weight: 52516.05

Authors

Duelli, A.,Kiss, B.,Lundholm, I.,Bodor, A.,Radnai, L.,Petoukhov, M.,Svergun, D.,Nyitray, L.,Katona, G. (deposition date: 2013-11-19, release date: 2014-05-07, Last modification date: 2023-12-20)

Primary citation

Duelli, A.,Kiss, B.,Lundholm, I.,Bodor, A.,Radnai, L.,Petoukhov, M.,Svergun, D.,Nyitray, L.,Katona, G.
The C-Terminal Random Coil Region Tunes the Ca2+-Binding Affinity of S100A4 Through Conformational Activation.
Plos One, 9:97654-, 2014

PubMed 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.

PubMed: 24830809
DOI: 10.1371/JOURNAL.PONE.0097654

Experimental method

X-RAY DIFFRACTION (1.37 Å)