10.1184/R1/6506753.v1
Hirsh Nanda
Hirsh
Nanda
Siddhartha A.K. Datta
Siddhartha A.K.
Datta
Frank Heinrich
Frank
Heinrich
Mathias Losche
Mathias
Losche
Alan Rein
Alan
Rein
Susan Krueger
Susan
Krueger
Joseph E. Curtis
Joseph E.
Curtis
Electrostatic Interactions and Binding Orientation of HIV-1 Matrix Studied by Neutron Reflectivity
Carnegie Mellon University
2010
Physics
2010-10-01 00:00:00
Journal contribution
https://kilthub.cmu.edu/articles/journal_contribution/Electrostatic_Interactions_and_Binding_Orientation_of_HIV-1_Matrix_Studied_by_Neutron_Reflectivity/6506753
<p>The N-terminal matrix (MA) domain of the HIV-1 Gag protein is responsible for binding to the plasma membrane of host cells during viral assembly. The putative membrane-binding interface of MA was previously mapped by means of mutagenesis and analysis of its trimeric crystal structure. However, the orientation of MA on membranes has not been directly determined by experimental measurements. We present neutron reflectivity measurements that resolve the one-dimensional scattering length density profile of MA bound to a biomimetic of the native viral membrane. A molecular refinement procedure was developed using atomic structures of MA to determine the orientation of the protein on the membrane. The orientation defines a lipid-binding interface consistent with previous mutagenesis results. The MA protein maintains this orientation without the presence of a myristate group, driven only by electrostatic interactions. Furthermore, MA is found to penetrate the membrane headgroup region peripherally such that only the side chains of specific Lys and Arg residues interact with the surface. The results suggest that electrostatic interactions are sufficient to favorably orient MA on viral membrane mimics. The spatial determination of the membrane-bound protein demonstrates the ability of neutron reflectivity to discern orientation and penetration under physiologically relevant conditions.</p>