Talk abstracts
Talk on Friday 01:15-01:30pm submitted by Jerricho Tipo
Dual conformational states of HIV-1 RRE stem-loop II and implications for the initial high-affinity Rev interaction
Jerricho Tipo (Department of Molecular and Cellular Biochemistry, Indiana University), Keerthi Gottipati (Department of Molecular and Cellular Biochemistry, Indiana University), Kay Choi (UTMB, Pharmacology and Toxicology; IU, Molecular and Cellular Biochemistry)
Abstract:
During HIV infection, intron-containing mRNA transcripts must exit the nucleus for the translation of late-stage HIV viral proteins and formation of HIV virions. To facilitate nuclear export, HIV uses a specific RNA sequence, the Rev response element (RRE), that is specifically recognized by the viral Rev protein (Regulator of viral expression). A single Rev initially binds a high-affinity site in stem-loop II, which promotes oligomerization of additional Rev proteins on RRE. The homo-oligomeric Rev-RRE ribonucleoprotein then recruits the nuclear export complex and intron-containing late-stage viral transcripts are subsequently shuttled into the cytoplasm. To better understand how RRE drives specific Rev interaction and subsequent oligomerization, we determined the crystal structure of RRE stem-loop II in distinct open and closed conformations. These structures show that the initial high-affinity Rev-binding site is located within the three-way junction rather than the predicted stem IIB. The closed and open conformers differ in their non-canonical interactions within the three-way junction, which lead to different rotations of the stems about the 3-way junction. Only the open conformation has a significant widening of the major groove capable of accommodating Rev interaction. Rev binding assays show that RRE stem-loop II has high- and low-affinity binding sites, each of which binds a Rev dimer. Based on results and previously published data, we propose a sequential binding model, wherein Rev-binding sites on RRE are sequentially created through structural rearrangements induced by Rev-RRE interactions.
References:
Can contact Kay Choi at Tel:812-855-1159; Email: kaychoi@iu.edu
Keywords: HIV, Rev-Response Element (RRE), structure