title: Role of RNA Branchedness in the Competition for Viral Capsid Proteins.
abstract: To optimize binding-and packaging-by their capsid proteins (CP), single-stranded (ss) RNA viral genomes often have local secondary/tertiary structures with high CP affinity, with these "packaging signals" serving as heterogeneous nucleation sites for the formation of capsids. Under typical in vitro self-assembly conditions, however, and in particular for the case of many ssRNA viruses whose CP have cationic N-termini, the adsorption of CP by RNA is nonspecific because the CP concentration exceeds the largest dissociation constant for CP-RNA binding. Consequently, the RNA is saturated by bound protein before lateral interactions between CP drive the homogeneous nucleation of capsids. But, before capsids are formed, the binding of protein remains reversible and introduction of another RNA species-with a different length and/or sequence-is found experimentally to result in significant redistribution of protein. Here we argue that, for a given RNA mass, the sequence with the highest affinity for protein is the one with the most compact secondary structure arising from self-complementarity; similarly, a long RNA steals protein from an equal mass of shorter ones. In both cases, it is the lateral attractions between bound proteins that determines the relative CP affinities of the RNA templates, even though the individual binding sites are identical. We demonstrate this with Monte Carlo simulations, generalizing the Rosenbluth method for excluded-volume polymers to include branching of the polymers and their reversible binding by protein.
authors.affiliation: Department of Chemistry and Biochemistry, UCLA , Los Angeles, California 90095, United States.|Institute of Chemistry and the Fritz Haber Research Center, The Hebrew University , Jerusalem, 91904 Israel.
authors.forename: Surendra W
authors.initials: SW
authors.lastname: Singaram
authors.affiliation: Department of Chemistry and Biochemistry, UCLA , Los Angeles, California 90095, United States.
authors.forename: Rees F
authors.initials: RF
authors.lastname: Garmann
authors.affiliation: Department of Chemistry and Biochemistry, UCLA , Los Angeles, California 90095, United States.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Knobler
authors.affiliation: Department of Chemistry and Biochemistry, UCLA , Los Angeles, California 90095, United States.
authors.forename: William M
authors.initials: WM
authors.lastname: Gelbart
authors.affiliation: Institute of Chemistry and the Fritz Haber Research Center, The Hebrew University , Jerusalem, 91904 Israel.
authors.forename: Avinoam
authors.initials: A
authors.lastname: Ben-Shaul
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D012328:RNA Viruses / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D036022:Capsid Proteins; D012367:RNA, Viral