title: Molecular dynamics simulation studies on Ca2+ -induced conformational changes of annexin I.
abstract: Cryo-electron microscopy (EM) and X-ray studies proposed different mechanisms for annexin-induced membrane aggregation. In this work, molecular dynamics (MD) simulation technique was utilized to gain an insight into the calcium-induced conformational changes on annexin I and their implication in membrane aggregation mechanism. MD simulations were performed on the Ca2+ -free annexin I with the N-terminal domain buried inside the core (System 1), the Ca2+ -bound annexin I without N-terminal domain (System 2) and the Ca2+ -bound annexin I with the N-terminal domain exposed (System 3). Our results indicated that calcium binding increases the flexibility of annexin I core domain residues including the calcium coordinating residues. As a result, annexin I was activated to interact with the negatively charged membrane. The exposed N-terminal domain was very flexible and gradually lost the secondary structure during MD simulation, suggesting that the N-terminal may adopt a favorable conformation to bind a second membrane and also explaining the failure of attempts to crystallize the full-length annexin I in the presence of calcium ions. The measured dimensions of the averaged simulation structure of the Ca2+ -bound annexin I with the N-terminal exposed (System 3) support the proposed membrane aggregation mechanism based on X-ray studies.
authors.affiliation: Department of Chemistry, East Carolina University, Greenville, NC 27858, USA.
authors.forename: Rohini D
authors.initials: RD
authors.lastname: Shesham
authors.forename: Libero J
authors.initials: LJ
authors.lastname: Bartolotti
authors.forename: Yumin
authors.initials: Y
authors.lastname: Li
mesh_terms: D017305:Annexin A1 / Q000737:chemistry* / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D003198:Computer Simulation; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D017305:Annexin A1; D002118:Calcium