Highly conserved extracellular residues mediate interactions between pore-forming and regulatory subunits of the yeast Ca channel related to the animal VGCC/NALCN family.

Yeasts and fungi generate Ca signals in response to environmental stresses through Ca channels essentially composed of Cch1 and Mid1. Cch1 is homologous to the pore-forming α subunit of animal voltage-gated Ca channels (VGCCs) and sodium leak channels nonselective (NALCNs), whereas Mid1 is a membrane-associated protein similar to the regulatory α/δ subunit of VGCCs and the regulatory subunit of NALCNs. Although the physiological roles of Cch1/Mid1 channels are known, their molecular regulation remains elusive, including subunit interactions regulating channel functionality.

A bipolar functionality of Q/N-rich proteins: Lsm4 amyloid causes clearance of yeast prions.

Prions are epigenetic modifiers that cause partially loss-of-function phenotypes of the proteins in Saccharomyces cerevisiae. The molecular chaperone network that supports prion propagation in the cell has seen a great progress in the last decade. However, the cellular machinery to activate or deactivate the prion states remains an enigma, largely due to insufficient knowledge of prion-regulating factors.

Clearance of yeast prions by misfolded multi-transmembrane proteins.

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the stress response to protect cells against toxicity by the unfolded protein response (UPR), heat shock response (HSR), and ER-associated degradation pathways. Here, we found that over-production of C-terminally truncated multi-transmembrane (MTM) mutant proteins triggers HSR, but not UPR, and clearance of yeast prions [PSI(+)] and [URE3]. One of the mutant MTM proteins, Dip5ΔC-v82, produces a disabled amino-acid permease.

A bipolar personality of yeast prion proteins.

Prions are infectious, self-propagating protein conformations. [PSI+], [RNQ+] and [URE3] are well characterized prions in Saccharomyces cerevisiae and represent the aggregated states of the translation termination factor Sup35, a functionally unknown protein Rnq1, and a regulator of nitrogen metabolism Ure2, respectively. Overproduction of Sup35 induces the de novo appearance of the [PSI+] prion in [RNQ+] or [URE3] strain, but not in non-prion strain.

[PSI(+)] aggregate enlargement in rnq1 nonprion domain mutants, leading to a loss of prion in yeast.

[PIN(+)] is the prion form of the Rnq1 protein of unknown function in Saccharomyces cerevisiae. A glutamine/asparagine (Q/N)-rich C-terminal domain is necessary for the propagation of [PIN(+)], whereas the N-terminal region is non-Q/N-rich and considered the nonprion domain. Here, we isolated numerous single-amino-acid mutations in Rnq1, phenotypically similar to Rnq1Δ100, which inhibit [PSI(+)] propagation in the [PIN(+)] state, but not in the [pin(-)] state, when overproduced.

Halogen bonds as orthogonal molecular interactions to hydrogen bonds.

Halogen bonds (X-bonds) are shown to be geometrically perpendicular to and energetically independent of hydrogen bonds (H-bonds) that share a common carbonyl oxygen acceptor. This orthogonal relationship is accommodated by the in-plane and out-of-plane electronegative potentials of the oxygen, which are differentially populated by H- and X-bonds. Furthermore, the local conformation of a peptide helps to define the geometry of the H-bond and thus the oxygen surface that is accessible for X-bonding.