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Megakaryoblastic leukemia 2 (MKL2)/myocardin‐related transcription factor‐B (MRTFB), a serum response factor (SRF) coactivator, is an important regulator of gene expression and neuronal morphology. Here, we show that different mouse MRTFB splice isoforms, including a novel fourth MRTFB isoform named spliced neuronal long isoform of SRF transcriptional coactivator (SOLOIST)/MRTFB isoform 4 (MRTFB i4), play distinct roles in this process. SOLOIST/MRTFB i4 has a short exon that encodes 21 amino acid residues ahead of the first RPXXXEL (RPEL) motif in MRTFB isoform 3. Quantitative PCR revealed that SOLOIST/MRTFB i4 and isoform 1 were enriched in the forebrain and neurons, and up‐regulated during brain development. Conversely, isoform 3 was detected in various tissues, including both neurons and astrocytes, and was down‐regulated in the developing brain. Reporter assays supported the SRF‐coactivator function of SOLOIST/MRTFB i4 as well as isoform 1. Acute expression of MRTFB isoform 1, but not isoform 3 or SOLOIST/MRTFB i4, in neuronal cells within 24 hr drastically increased endogenous immediate early gene [c‐fos, egr1, and activity‐regulated cytoskeleton‐associated protein] expression, but not endogenous actinin α1, β‐actin, gelsolin, or srf gene expression measured by qPCR. Over‐expression of SOLOIST/MRTFB i4 reduced the dendritic complexity of cortical neurons, whereas over‐expression of isoform 1 increased this complexity. Co‐expression of isoform 1 and SOLOIST/MRTFB i4 in cortical neurons revealed that isoform 1 competitively counteracted down‐regulation by SOLOIST/MRTFB i4. Our findings indicate that MRTFB isoforms have unique expression patterns and differential effects on gene expression and dendritic complexity, which contribute to shaping neuronal circuits, at least in part. [ABSTRACT FROM AUTHOR]

Patients with transthyretin (TTR)‐type familial amyloid polyneuropathy (FAP) typically exhibit sensory dominant polyneuropathy and autonomic neuropathy. However, the molecular pathogenesis of the neuropathy remains unclear. In this study, we characterize the features of FAP TTR the substitution of lysine for glutamic acid at position 61 (E61K). This FAP was late‐onset, with sensory dominant polyneuropathy, autonomic neuropathy, and cardiac amyloidosis. Interestingly, no amyloid deposits were found in the endoneurium of the four nerve specimens examined. Therefore, we examined the amyloidogenic properties of E61K TTR in vitro. Recombinant wild‐type TTR, the substitution of methionine for valine at position 30 (V30M) TTR, and E61K TTR proteins were incubated at 37°C for 72 hr, and amyloid fibril formation was assessed using the thioflavin‐T binding assay. Amyloid fibril formation by E61K TTR was less than that by V30M TTR, and similar to that by wild‐type TTR. E61K TTR did not have an inhibitory effect on neurite outgrowth from adult rat dorsal root ganglion (DRG) neurons, but V30M TTR did. Furthermore, we studied the sural nerve of our patient by terminal deoxynucleotidyl transferase dUTP nick end labeling and electron microscopy. A number of apoptotic cells were observed in the endoneurium of the nerve by transferase dUTP nick end labeling. Chromatin condensation was confirmed in the nucleus of non‐myelinating Schwann cells by electron microscopy. These findings suggest that E61K TTR is low amyloidogenic, in vitro and in vivo. However, TTR aggregates and amyloid fibrils in the DRG may cause sensory impairments in FAP because the DRG has no blood–nerve barrier. Moreover, Schwann cell apoptosis may contribute to the neurodegeneration. [ABSTRACT FROM AUTHOR]

SIRT5, one of the mammalian sirtuins, specifically recognizes succinyl‐lysine residues on proteins and catalyzes the desuccinylation reaction. In this study, we characterized SIRT5 mutants with hydrophobic amino acid substitutions at Q140 and N141, in addition to the catalytic residue H158, known as an active site residue, by the Michaelis–Menten analysis and X‐ray crystallography. Kinetic analysis showed that the catalytic efficiency (kcat/Km) of the Q140L and N141V mutants decreased to 0.02 times and 0.0038 times that of the wild‐type SIRT5, respectively, with the activity of the N141V mutant becoming comparable to that of the H158M mutant. Our findings indicate that N141 contributes significantly to the desuccinylation reaction. [ABSTRACT FROM AUTHOR]

The peptides of silkworm FMBP-1 STPR (sSTPR), a 23-amino acid tandem repeat domain, and human ZNF821 STPR (hSTPR) are prepared and their DNA binding behaviors are compared. STPR sequences are found in many proteins from vertebrates, insects and nematodes and some of the consensus amino acid residues is responsible for DNA binding and concomitant has increased in [alpha]-helix structure content.

The crystal structure of the epigallocatechin 3-gallate-transthyretin (EGCG-V30M TTR) complex was characterized to demonstrate that EGCG as the major polyphenol component of green tea binds to TTR and suppresses TTR amyloid fibril formation. The study provides insight into the possible application of EGCG as a candidate compound for familial amyloid polyneuropathy (FAP) therapy.

A study was conducted to analyze the crystal structure and biochemical and biophysical properties of two variants E54G and E54K from transthyretin (TTR) which is a tetrameric protein associated with amyloidosis caused by tetramer dissociation and monomer misfolding. The low tetramer stability and more fibril formation in E54K and E54G TTRs than in wild-type TTR

A study was conducted to examine the structure of the N-terminal fragment of big defensin in a micellar solution. Findings showed that the fragment peptide forms a single [alpha]-helix structure.

The article presents a comparative study of the different strategies used by the big defensin and other [beta]-defensin structure for suppressing the growth of the Gram-positive bacteria. Big defensin is shown to exhibit a closely packed single-globule conformation, the structure of which can be divided into the N- and C-terminal domains.

The solution structure of diapause-specific peptide (DSP) isolated from the beetle leaf is studied to understand the half-cystine pair residues forming disulfide bonds. The functional role of DSP could help to derive useful peptides with antifungal and [Ca.sup.2+] channel inhibitory activities.

The structure and stability of a human Ser112Ile transthyretin variant is investigated and demonstrated that the Ser112Ile variant exists as a dimer having nonnative tertiary structure at physiological pH. The results describe the importance of an unstable dimeric structure in forming spherical aggregates that induces cell death in a human neuroblastoma cell line.

The mutation in the monomer-monomer and dimer-dimer interaction site of the transthyretin tetramer is described. The results indicate that unfolding of Y114H and Y116S is less cooperative than wild-type transthyretin.