Structural Biochemistry/Viruses and SLiMs Interaction/Viral Pathways/Utilizing Cellular Transport

Utilizing Cellular Transport
The cell transports proteins to specific cellular compartments through large molecular complexes such as the nuclear pore or vast cytoskeletal structures such as microtubules. This is how the cell arranges and constructs localization and movement of proteins. Viruses can take advantage of this cellular transport pathway by imitating the motifs that govern the transport system. A paradigm of this concept is shown in targeting signal mimicry of the “motif-driven nuclear shutting of the essential regulatory protein Rev of HIV”. Rev consists of “both a non-canonical nuclear localization signal (NLS) (RRNRRRRWRER38) and a nuclear export signal (NES) (LxxLxxLxL75)”. The non-canonical nuclear localizsation signal encompasses an RNA-binding motif protein and acts as a switch for molecular functions. When the non-canonical nuclear localization signal is bound that the motif, the nuclear export signal is the only motif that is free for use and RNA is exported is dissociated. Once a sufficient amount of RNA has been exported and dissociated, then the non-canonical nuclear localization signal becomes readily available to allow nuclear import into the cell. These two motifs are important for the mechanism that separates the “early and late phases of the HIV life cycle; in the absence of Rev, nuclear mRNA is quickly spliced to produce accessory proteins (including Rev itself)”. The construction of motifs in Rev governs the outflow of unspliced and partially spliced mRNA, allowing the creation of late phase proteins that are needed for the virus to accumulate.