6YNS

CaM-P458 complex (crystal form 2)

6YNS の概要

• エントリーDOI: 10.2210/pdb6yns/pdb
• 分子名称: Calmodulin-1, Bifunctional adenylate cyclase toxin/hemolysin CyaA, CALCIUM ION (3 entities in total)
• 機能のキーワード: toxin, cyaa, metal binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 36
• 化学式量合計: 261887.92

構造登録者

Mechaly, A.E.,Voegele, A.,Haouz, A.,Chenal, A. (登録日: 2020-04-14, 公開日: 2021-03-17, 最終更新日: 2024-01-24)

主引用文献

Voegele, A.,Sadi, M.,O'Brien, D.P.,Gehan, P.,Raoux-Barbot, D.,Davi, M.,Hoos, S.,Brule, S.,Raynal, B.,Weber, P.,Mechaly, A.,Haouz, A.,Rodriguez, N.,Vachette, P.,Durand, D.,Brier, S.,Ladant, D.,Chenal, A.
A High-Affinity Calmodulin-Binding Site in the CyaA Toxin Translocation Domain is Essential for Invasion of Eukaryotic Cells.
Adv Sci, 8:2003630-2003630, 2021

PubMed Abstract: The molecular mechanisms and forces involved in the translocation of bacterial toxins into host cells are still a matter of intense research. The adenylate cyclase (CyaA) toxin from displays a unique intoxication pathway in which its catalytic domain is directly translocated across target cell membranes. The CyaA translocation region contains a segment, P454 (residues 454-484), which exhibits membrane-active properties related to antimicrobial peptides. Herein, the results show that this peptide is able to translocate across membranes and to interact with calmodulin (CaM). Structural and biophysical analyses reveal the key residues of P454 involved in membrane destabilization and calmodulin binding. Mutational analysis demonstrates that these residues play a crucial role in CyaA translocation into target cells. In addition, calmidazolium, a calmodulin inhibitor, efficiently blocks CyaA internalization. It is proposed that after CyaA binding to target cells, the P454 segment destabilizes the plasma membrane, translocates across the lipid bilayer and binds calmodulin. Trapping of CyaA by the CaM:P454 interaction in the cytosol may assist the entry of the N-terminal catalytic domain by converting the stochastic motion of the polypeptide chain through the membrane into an efficient vectorial chain translocation into host cells.

PubMed: 33977052
DOI: 10.1002/advs.202003630

実験手法

X-RAY DIFFRACTION (3.94 Å)