5LPX

Crystal structure of PKC phosphorylation-mimicking mutant (S26E) Annexin A2

Summary for 5LPX

• Entry DOI: 10.2210/pdb5lpx/pdb
• Related: 5LPU
• Descriptor: Annexin A2, CALCIUM ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: calcium binding protein, protein-protein complex, phospho-mimickation
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted, extracellular space, extracellular matrix, basement membrane : P07355
• Total number of polymer chains: 1
• Total formula weight: 39040.56

Authors

Ecsedi, P.,Gogl, G.,Kiss, B.,Nyitray, L. (deposition date: 2016-08-15, release date: 2017-07-05, Last modification date: 2024-11-06)

Primary citation

Ecsedi, P.,Kiss, B.,Gogl, G.,Radnai, L.,Buday, L.,Koprivanacz, K.,Liliom, K.,Leveles, I.,Vertessy, B.,Jeszenoi, N.,Hetenyi, C.,Schlosser, G.,Katona, G.,Nyitray, L.
Regulation of the Equilibrium between Closed and Open Conformations of Annexin A2 by N-Terminal Phosphorylation and S100A4-Binding.
Structure, 25:1195-1207.e5, 2017

PubMed Abstract: Annexin A2 (ANXA2) has a versatile role in membrane-associated functions including membrane aggregation, endo- and exocytosis, and it is regulated by post-translational modifications and protein-protein interactions through the unstructured N-terminal domain (NTD). Our sequence analysis revealed a short motif responsible for clamping the NTD to the C-terminal core domain (CTD). Structural studies indicated that the flexibility of the NTD and CTD are interrelated and oppositely regulated by Tyr24 phosphorylation and Ser26Glu phosphomimicking mutation. The crystal structure of the ANXA2-S100A4 complex showed that asymmetric binding of S100A4 induces dislocation of the NTD from the CTD and, similar to the Ser26Glu mutation, unmasks the concave side of ANXA2. In contrast, pTyr24 anchors the NTD to the CTD and hampers the membrane-bridging function. This inhibition can be restored by S100A4 and S100A10 binding. Based on our results we provide a structural model for regulation of ANXA2-mediated membrane aggregation by NTD phosphorylation and S100 binding.

PubMed: 28669632
DOI: 10.1016/j.str.2017.06.001

Experimental method

X-RAY DIFFRACTION (1.9 Å)