Analysis of Human Immunodeficiency Virus Type 1 Gag Dimerization-Induced Assembly Export

@article{citeulike:436346, abstract = {The nucleocapsid (NC) domains of retrovirus precursor Gag (PrGag) proteins play an essential role in virus assembly. Evidence suggests that NC binding to viral RNA promotes dimerization of PrGag capsid (CA) domains, which triggers assembly of CA N-terminal domains (NTDs) into hexamer rings that are interconnected by CA C-terminal domains. To examine the influence of dimerization on human immunodeficiency virus type 1 (HIV-1) Gag protein assembly in vitro, we analyzed the assembly properties of Gag proteins in which NC domains were replaced with cysteine residues that could be linked via chemical treatment. In accordance with the model that Gag protein pairing triggers assembly, we found that cysteine cross-linking or oxidation reagents induced the assembly of virus-like particles. However, efficient assembly also was observed to be temperature dependent or required the tethering of NTDs. Our results suggest a multistep pathway for HIV-1 Gag protein assembly. In the first step, Gag protein pairing through NC-RNA interactions or C-terminal cysteine linkage fosters dimerization. Next, a conformational change converts assembly-restricted dimers or small oligomers into assembly-competent ones. At the final stage, final particle assembly occurs, possibly through a set of larger intermediates.}, author = {Alfadhli, Ayna and Dhenub, Tenzin C. and Still, Amelia and Barklis, Eric}, citeulike-article-id = {436346}, citeulike-linkout-0 = {http://dx.doi.org/10.1128/JVI.79.23.14498}, citeulike-linkout-1 = {http://jvi.asm.org/cgi/content/abstract/79/23/14498}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16282449}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16282449}, day = {1}, doi = {10.1128/JVI.79.23.14498}, journal = {J. Virol.}, keywords = {assembly, gag, hiv}, month = {December}, number = {23}, pages = {14498--14506}, posted-at = {2005-12-12 20:24:40}, priority = {2}, title = {Analysis of Human Immunodeficiency Virus Type 1 Gag Dimerization-Induced Assembly}, url = {http://dx.doi.org/10.1128/JVI.79.23.14498}, volume = {79}, year = {2005} }

TY - JOUR ID - citeulike:436346 L3 - citeulike-article-id:436346 N2 - The nucleocapsid (NC) domains of retrovirus precursor Gag (PrGag) proteins play an essential role in virus assembly. Evidence suggests that NC binding to viral RNA promotes dimerization of PrGag capsid (CA) domains, which triggers assembly of CA N-terminal domains (NTDs) into hexamer rings that are interconnected by CA C-terminal domains. To examine the influence of dimerization on human immunodeficiency virus type 1 (HIV-1) Gag protein assembly in vitro, we analyzed the assembly properties of Gag proteins in which NC domains were replaced with cysteine residues that could be linked via chemical treatment. In accordance with the model that Gag protein pairing triggers assembly, we found that cysteine cross-linking or oxidation reagents induced the assembly of virus-like particles. However, efficient assembly also was observed to be temperature dependent or required the tethering of NTDs. Our results suggest a multistep pathway for HIV-1 Gag protein assembly. In the first step, Gag protein pairing through NC-RNA interactions or C-terminal cysteine linkage fosters dimerization. Next, a conformational change converts assembly-restricted dimers or small oligomers into assembly-competent ones. At the final stage, final particle assembly occurs, possibly through a set of larger intermediates. IS - 23 JF - J. Virol. EP - 14506 TI - Analysis of Human Immunodeficiency Virus Type 1 Gag Dimerization-Induced Assembly VL - 79 SP - 14498 KW - assembly KW - gag KW - hiv AU - Alfadhli, Ayna AU - Dhenub, Tenzin AU - Still, Amelia AU - Barklis, Eric PY - 2005/12/01/ UR - http://dx.doi.org/10.1128/JVI.79.23.14498 ER -