The HIV-1 matrix (MA) protein 
is synthesized as part of the Pr55 Gag polyprotein that is cleaved to mature products during viral maturation. As part of Gag, MA is involved in virion assembly. The MA cleavage product is a component of the mature virion and enters infected cells along with viral RNA and other viral proteins. After reverse transcription, the viral RNA is associated with a large nucleoprotein complex called the preintegration complex (PIC) that is derived from the core of the infecting virion 
. Viral proteins reported to be associated with the PIC include integrase (IN), reverse transcriptase (RT), capsid (CA), Vpr, and MA.
Integrase within the PIC plays an essential role in integrating the viral DNA into the host genome, but the function of other proteins is less clearly understood; some may simply be left over from the infecting virion and play no further role in viral replication. The role of MA has been particularly controversial. Peptides spanning the highly basic amino acids 25–33 of MA function as a nuclear localization signal (NLS) when fused to a reporter protein and it has been proposed that this NLS facilitates nuclear import of the PIC 
. However, subsequent studies slowed this putative NLS in MA is not essential for HIV-1 replication in non-dividing cells 
and therefore is not essential for nuclear import of the PIC. Nevertheless, the N-terminal basic region of MA does seem to be required for maximum infectivity. Mutation of the N-terminal basic region of MA impairs infectivity and decreases circularization of viral DNA 
. Although circular viral DNA is a dead end product that is not on the integration pathway, the effect of these mutations indicates that MA is functionally associated with the PIC and can influence the viral replication pathway after reverse transcription. Regardless of the function of MA for the PIC, its presence within the complex implies interaction with other components of the complex. MA binds DNA and binding requires the N-terminal basic region
. A direct interaction of MA and DNA may therefore account for its retention within the PIC. In this paper we use solution NMR spectroscopy to probe the interactions between MA and DNA. Using chemical shift perturbation mapping we confirm that MA interacts with DNA and identify the DNA binding surface of MA. Using paramagnetic resonance enhancement (PRE) measurements, we demonstrate that the interaction between MA and DNA is non-specific. The relative of orientation of MA on the DNA in the complex was ascertained from residual dipolar coupling measurements, and this data, together with the chemical shift perturbation map, allowed us to generate a model of the complex.