Bending-Twisting Motions and Main Interactions in Nucleoplasmin Nuclear Import

Author(s)

Geraldo, Marcos Tadeu ^[1] ; Sekijima Takeda, Agnes Alessandra ^{[1, 2]} ; Kimus Braz, Antonio Sergio ^[3] ; Lemke, Ney ^[1]

Affiliation

^[1] UNESP Univ Estadual Paulista, Dept Fis & Biofis, Lab Bioinformat & Biofis Computac, Inst Biociencias Botucatu, BR-18618970 Botucatu, SP - Brazil

^[2] UNESP Univ Estadual Paulista, Inst Biotecnol IBTEC, BR-18607440 Botucatu, SP - Brazil

^[3] UFABC Univ Fed ABC, Lab Biol Computac & Bioinformat, Ctr Ciencias Nat & Humanas, BR-09210170 Santo Andre, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 11, n. 6 JUN 3 2016.
• Web of Science Citations: 2

Abstract

Alpha solenoid proteins play a key role in regulating the classical nuclear import pathway, recognizing a target protein and transporting it into the nucleus. Importin-alpha (Imp alpha) is the solenoid responsible for cargo protein recognition, and it has been extensively studied by Xray crystallography to understand the binding specificity. To comprehend the main motions of Imp alpha and to extend the information about the critical interactions during carrier-cargo recognition, we surveyed different conformational states based on molecular dynamics (MD) and normal mode (NM) analyses. Our model of study was a crystallographic structure of Imp alpha complexed with the classical nuclear localization sequence (cNLS) from nucleoplasmin (Npl), which was submitted to multiple 100 ns of MD simulations. Representative conformations were selected for calculating the 87 lowest frequencies NMs of vibration, and a displacement approach was applied along each NM. Based on geometric criteria, using the radius of curvature and inter-repeat angles as the reference metrics, the main motions of Imp alpha were described. Moreover, we determined the salt bridges, hydrogen bonds and hydrophobic interactions in the Imp alpha-NplNLS interface. Our results show the bending and twisting motions participating in the recognition of nuclear proteins, allowing the accommodation and adjustment of a classical bipartite NLS sequence. The essential contacts for the nuclear import were also described and were mostly in agreement with previous studies, suggesting that the residues in the cNLS linker region establish important contacts with Imp alpha adjusting the cNLS backbone. The MD simulations combined with NM analysis can be applied to the Imp alpha-NLS system to help understand interactions between Imp alpha and cNLSs and the analysis of non-classic NLSs. (AU)

• FAPESP's process: 14/21976-9 - Interaction of Ku70NLS and Importin-alpha based on molecular dynamics with excited normal modes (MDeNM)
• Grantee: Marcos Tadeu Geraldo
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 12/19447-2 - Dynamics of the interaction between Ku70NLS and Importin-alpha in the classical nuclear import pathway
• Grantee: Marcos Tadeu Geraldo
• Support Opportunities: Scholarships in Brazil - Doctorate