An image of the structure of hnRNP A1, a human protein that is key in viral replication, as it binds to RNA, has been captured by researchers, according to findings published in the Journal of Molecular Biology.
Blanton Tolbert, PhD, a chemistry professor at Case Western Reserve, Christopher E. Morgan, PhD, and Jennifer L Meagher, PhD and other colleagues from Case Western Reserve University and the University of Michigan snapped the images of hnRNP A1 as it binded with RNA. Dubbed the “hairpin loop,” the researchers described this particular binding RNA mechanism as different than the previously-known mechanisms of binding with DNA. Hairpin binding proteins recognize the sequence and structure of the hairpin loop, which DNA does not recognize, the researchers explained.
Building on prior knowledge that hnRNP A1 needs to connect both its domains, RRM1 and RRM2, to RNA, researchers noted that RRM1 alone connects with RNA while RRM2 supports and organizes RRM1 into its proper shape for the particular section of the loop. The researchers changed amino acids on domain surfaces to confirm their findings.
Mutations on the non-contact side of RRM1 resulted in decoupling and caused weakness in RNA affinity. Without this connection, the researchers noted that RRM1 did not create the hairpin loop.
“The biophysical implications of the structural model were tested by measuring kinetic binding parameters, where mutations introduced within the apical loop reduce binding affinities by slowing down the rate of complex formation. Collectively, the data presented here provide the first insights into hnRNP A1–RNA interactions,” the study researchers noted.
The researchers said further study into these mechanisms of action may reveal how viruses like HIV and others commandeer proteins and offer clues to prevent viruses from replicating. They are looking into developing antagonistic agents that would disrupt the interaction of the protein with viruses.
1. Morgan CE, Meagher JL, Levengood JD, et al. The first crystal structure of the UP1 domain of hnRNP A1 bound to RNA reveals a new look for an old RNA binding protein. J Mol Bio. 2015;427(20):3241-3257. DOI:10.1016/j.jmb.2015.05.009