Structural characterization of membrane-bound human immunodeficiency virus-1 Gag matrix with neutron reflectometry

The structural characterization of peripheral membrane proteins represents a tremendous challenge in structural biology due to their transient interaction with the membrane and the potential multitude of protein conformations during this interaction. Neutron reflectometry is uniquely suited to address this problem because of its ability to structurally characterize biological model systems nondestructively and under biomimetic conditions that retain full protein functionality. Being sensitive to only the membrane-bound fraction of a water-soluble peripheral protein, neutron reflectometry obtains a low-resolution average structure of the protein-membrane complex that is further refined using integrative modeling strategies. Here, the authors review the current technological state of biological neutron reflectometry exemplified by a detailed report on the structure determination of the myristoylated human immunodeficiency virus-1 (HIV-1) Gag matrix associated with phosphoserine-containing model membranes. The authors found that the HIV-1 Gag matrix is able to adopt different configurations at the membrane in a pH-dependent manner and that the myristate group orients the protein in a way that is conducive to PIP(2)-binding.