Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data

and Computer Simulations

Saturday Speaker Abstracts

Structural Insights into the Architecture of Human Importin4_Histone H3/H4_Asf1a

Complex and Its Histone H3 Tail Binding

Jungmin Yoon,

Ji-Joon Song

Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.

Importin4 is responsible for transporting histone H3 and H4 in complex with the histone

chaperone Asf1a to the nucleus for de novo chromatin assembly. Importin4 recognizes the

nuclear localization sequence (NLS) located at the N-terminal tails of histones. Here, we

analyzed the structure and interactions of human Importin4, histones and the histone chaperone

Asf1a by cross-linking mass spectrometry (XL-MS), X-ray crystallography, negative-stain

electron microscopy (EM), small-angle X-ray scattering and integrative modeling. The XL-MS

data showed that the C-terminal region of Importin4 interacts exclusively with the N-terminal

tails of histone H3. We determined the crystal structure of the C-terminal part of Importin4

bound with histone H3 tail, thus revealing that the acidic path in Importin4 accommodates

histone H3 NLS and that histone H3 Lys14 is the primary residue interacting with Importin4.

Furthermore, we present the structure of the Importin4_Histone H3/H4_Asf1a complex

computed through an integrative modeling approach. Overall, this work provides structural

insights into how Importin4 recognizes histones and their chaperone complex.

Incorporating Experimental Data in Long Timescales Macromolecular Simulations

Cecilia Clementi

Rice University, Houston, TX, USA

No Abstract