Gluon confinement criterion in QCD

We fix exactly and uniquely the infrared structure of the full gluon propagator in QCD, not solving explicitly the corresponding dynamical equation of motion. By construction, this structure is an infinite sum over all possible severe (i.e., more singular than $1/q^2$) infrared singularities. It reflects the zero momentum modes enhancement effect in the true QCD vacuum, which is due to the self-interaction of massless gluons. It existence automatically exhibits a characteristic mass (the so-called mass gap). It is responsible for the scale of nonperturbative dynamics in the true QCD ground state. The theory of distributions, complemented by the dimensional regularization method, allows one to put the severe infrared singularities under the firm mathematical control. By an infrared renormalization of a mass gap only, the infrared structure of the full gluon propagator is exactly reduced to the simplest severe infrared singularity, the famous $(q^2)^{-2}$. Thus we have exactly established the interaction between quarks (concerning its pure gluon (i.e., nonlinear) contribution) up to its unimportant perturbative part. This also makes it possible for the first time to formulate the gluon confinement criterion and intrinsically nonperturbative phase in QCD in a manifestly gauge-invariant ways.Comment: 10 pages, no figures, no tables. Typos corrected and the clarification is intoduced. Shorten version to appear in Phys. Lett.

Comment on "Protein assemblies ejected directly from native membranes yield complexes for mass spectrometry".

Chorev et al (Reports, 16 November 2018, p. 829) describe mass spectrometry on mitochondrial membrane proteins ionized directly from their native environment. However, the assignments made to measured masses are incorrect or inconclusive and lack experimental validation. The proteins are not in their "native" condition: They have been stripped of tightly bound lipids, and the complexes are fragmented or in physiologically irrelevant oligomeric states

The substrate specificity of mitochondrial carriers: Mutagenesis revisited

Mitochondrial carriers transport inorganic ions, nucleotides, amino acids, keto acids and cofactors across the mitochondrial inner membrane. Structurally they consist of three domains, each containing two transmembrane alpha-helices linked by a short alpha-helix and loop. The substrate binds to three major contact points in the central cavity. The class of substrate (e.g., adenine nucleotides) is determined by contact point II on transmembrane alpha-helix H4 and the type of substrate within the class (e.g., ADP, coenzyme A) by contact point I in H2, whereas contact point III on H6 is most usually a positively charged residue, irrespective of the type or class. Two salt bridge networks, consisting of conserved and symmetric residues, are located on the matrix and cytoplasmic side of the cavity. These residues are part of the gates that are involved in opening and closing of the carrier during the transport cycle, exposing the central substrate binding site to either side of the membrane in an alternating way. Here we revisit the plethora of mutagenesis data that have been collected over the last two decades to see if the residues in the proposed binding site and salt bridge networks are indeed important for function. The analysis shows that the major contact points of the substrate binding site are indeed crucial for function and in defining the specificity. The matrix salt bridge network is more critical for function than the cytoplasmic salt bridge network in agreement with its central position, but neither is likely to be involved in substrate recognition directly

The yeast mitochondrial pyruvate carrier is a hetero-dimer in its functional state.

The mitochondrial pyruvate carrier (MPC) is critical for cellular homeostasis, as it is required in central metabolism for transporting pyruvate from the cytosol into the mitochondrial matrix. MPC has been implicated in many diseases and is being investigated as a drug target. A few years ago, small membrane proteins, called MPC1 and MPC2 in mammals and Mpc1, Mpc2 and Mpc3 in yeast, were proposed to form large protein complexes responsible for this function. However, the MPC complexes have never been isolated and their composition, oligomeric state and functional properties have not been defined. Here, we identify the functional unit of MPC from Saccharomyces cerevisiae In contrast to earlier hypotheses, we demonstrate that MPC is a hetero-dimer, not a multimeric complex. When not engaged in hetero-dimers, the yeast Mpc proteins can also form homo-dimers that are, however, inactive. We show that the earlier described substrate transport properties and inhibitor profiles are embodied by the hetero-dimer. This work provides a foundation for elucidating the structure of the functional complex and the mechanism of substrate transport and inhibition.This work was supported by the Medical Research Council Grant MC_UU_00015/1 (to E.R.S.K.), the Swiss National Science Foundation 31003A_179421/1 (to J-C.M.) and the Oncosuisse grant KFS-4434-02-2018 (to J-C.M.)

Structural insight into mitochondrial β-barrel outer membrane protein biogenesis.

In mitochondria, -barrel outer membrane proteins mediate protein import, metabolite transport, lipid transport, and biogenesis. The Sorting and Assembly Machinery (SAM) complex consists of three proteins that assemble as a 1:1:1 complex to fold -barrel proteins and insert them into the mitochondrial outer membrane. We report cryoEM structures of the SAM complex from Myceliophthora thermophila, which show that Sam50 forms a 16-stranded transmembrane -barrel with a single polypeptide-transport associated (POTRA) domain extending into the intermembrane space. Sam35 and Sam37 are located on the cytosolic side of the outer membrane, with Sam35 capping Sam50, and Sam37 interacting extensively with Sam35. Sam35 and Sam37 each adopt a GST-like fold, with no functional, structural, or sequence similarity to their bacterial counterparts. Structural analysis shows how the Sam50 barrel opens a lateral gate to accommodate its substrates

Transporter gene acquisition and innovation in the evolution of Microsporidia intracellular parasites.

The acquisition of genes by horizontal transfer can impart entirely new biological functions and provide an important route to major evolutionary innovation. Here we have used ancient gene reconstruction and functional assays to investigate the impact of a single horizontally transferred nucleotide transporter into the common ancestor of the Microsporidia, a major radiation of intracellular parasites of animals and humans. We show that this transporter provided early microsporidians with the ability to steal host ATP and to become energy parasites. Gene duplication enabled the diversification of nucleotide transporter function to transport new substrates, including GTP and NAD+, and to evolve the proton-energized net import of nucleotides for nucleic acid biosynthesis, growth and replication. These innovations have allowed the loss of pathways for mitochondrial and cytosolic energy generation and nucleotide biosynthesis that are otherwise essential for free-living eukaryotes, resulting in the highly unusual and reduced cells and genomes of contemporary Microsporidia

Structural insight into mitochondrial β-barrel outer membrane protein biogenesis

Abstract: In mitochondria, β-barrel outer membrane proteins mediate protein import, metabolite transport, lipid transport, and biogenesis. The Sorting and Assembly Machinery (SAM) complex consists of three proteins that assemble as a 1:1:1 complex to fold β-barrel proteins and insert them into the mitochondrial outer membrane. We report cryoEM structures of the SAM complex from Myceliophthora thermophila, which show that Sam50 forms a 16-stranded transmembrane β-barrel with a single polypeptide-transport-associated (POTRA) domain extending into the intermembrane space. Sam35 and Sam37 are located on the cytosolic side of the outer membrane, with Sam35 capping Sam50, and Sam37 interacting extensively with Sam35. Sam35 and Sam37 each adopt a GST-like fold, with no functional, structural, or sequence similarity to their bacterial counterparts. Structural analysis shows how the Sam50 β-barrel opens a lateral gate to accommodate its substrates