Caspar carboxylates: the structural basis of tobamovirus disassembly.

Carboxylate groups have been known for many years to drive the disassembly of simple viruses, including tobacco mosaic virus (TMV). The identities of the carboxylate groups involved and the mechanism by which they initiate disassembly have not, however, been clear. Structures have been determined at resolutions between 2.9 and 3.5 A for five tobamoviruses by fiber diffraction methods. Site-directed mutagenesis has also been used to change numerous carboxylate side chains in TMV to the corresponding amides. Comparison of the stabilities of the various mutant viruses shows that disassembly is driven by a much more complex set of carboxylate interactions than had previously been postulated. Despite the importance of the carboxylate interactions, they are not conserved during viral evolution. Instead, it appears that during evolution, patches of electrostatic interaction drift across viral subunit interfaces. The flexibility of these interactions confers a considerable advantage on the virus, enabling it to change its surface structure rapidly and thus evade host defenses

Physical mapping of male fertility and meiotic drive quantitative trait loci in the mouse t complex using chromosome deficiencies [In Process Citation]

The t complex spans 20 cM of the proximal region of mouse chromosome 17. A variant form, the t haplotype (t), exists at significant frequencies in wild mouse populations and is characterized by the presence of inversions that suppress recombination with wild-type (+) chromosomes. Transmission ratio distortion and sterility are associated with t and affect males only. It is hypothesized that these phenomena are caused by trans-acting distorter/sterility factors that interact with a responder locus (Tcr(t)) and that the distorter and sterility factors are the same because homozygosity of the distorters causes male sterility. One factor, Tcd1, was previously shown to be amorphic using a chromosome deletion. To overcome limitations imposed by recombination suppression, we used a series of deletions within the t complex in trans to t chromosomes to characterize the Tcd1 region. We find that the distorter activity of Tcd1 is distinct from a linked sterility factor, originally called tcs1. YACs mapped with respect to deletion breakpoints localize tcs1 to a 1.1-Mb interval flanked by D17Aus9 and Tctex1. We present evidence for the existence of multiple proximal t complex regions that exhibit distorter activity. These studies demonstrate the utility of chromosome deletions for complex trait analysis

Mutations in Serac1 or Synj2 cause proximal t haplotype-mediated male mouse sterility but not transmission ratio distortion.

Transmission ratio distortion (TRD) and sterility are male-specific quantitative trait phenomena associated with the mouse t haplotype. TRD occurs in t haplotype-heterozygous males and is caused by the deleterious action of distorter products on sperm bearing a wild-type responder locus. It has been proposed that t-mediated male sterility is a severe manifestation of TRD caused by homozygosity for distorter loci; thus, the distorter and sterility loci would be identical. In this, study a transgenic approach was used to identify the proximal sterility locus, tcs1 (S1), and test its role in TRD. Mice transgenic for a wild-type bacterial artificial chromosome (BAC) derived from the S1-critical region were bred onto t haplotype backgrounds. Mating results conclusively showed that the BAC is sufficient to restore fertility in otherwise sterile males. Multiple mutations were identified in the t alleles of Synj2 and Serac1, two genes in the BAC; thus, they are candidates for S1. In addition, whereas the BAC transgene rescued sterility, it had no effect on TRD. These results uncouple the proximal t haplotype sterility locus, S1, from TRD, demonstrating that S1 and the proximal distorter locus, D1, are not the same gene

Mutations of the mouse Twist and sy (fibrillin 2) genes induced by chemical mutagenesis of ES cells.

A prior phenotype-based screen of mice derived from ethylmethanesulfonate-mutagenized embryonic stem cells yielded two mouse limb defect mutants. Animals heterozygous for the polydactyly ems (Pde) mutation display preaxial polydactyly of the hindlimbs, and homozygous syndactyly ems (sne) animals are characterized by a fusion of the middle digits of their hindlimbs and sometimes forelimbs. We now report that Pde is a new allele of the basic helix-loop-helix protein gene Twist. Sequencing the full-length cDNA and several hundred basepairs of genomic DNA upstream of the coding region failed to reveal a mutation, suggesting that the lesion may be in a regulatory element of the gene. sne is a new fused phalanges (fp) allele of the shaker-with-syndactylism deletion complex (sy), and we show that the genomic lesion is a small deletion removing an entire exon, coincident with the insertion of the 3\u27 end of a LINE element belonging to the TF subfamily. Copyright 200