Molecular biology of distal muscular dystrophies—Sarcomeric proteins on top

During the last 10 years several muscular dystrophies within the group of distal myopathies have been clarified as to the molecular genetic cause of the disease. Currently, the next steps are carried out to identify the molecular pathogenesis downstream of the gene defects. Some early ideas on what is going on in the muscle cells based on the defect proteins are emerging. However, in no single distal muscular dystrophy these efforts have yet reached the point where direct trials for therapy would have been launched, and in many distal dystrophies the causative gene is still lacking. When comparing the gene defects in the distal dystrophies with the more common proximal muscular dystrophies such as dystrophinopathies or limb-girdle muscular dystrophies, there is a striking difference: the genes for distal dystrophies encode sarcomere proteins whereas the genes for proximal dystrophies more often encode sarcolemmal proteins.     

昆虫包涵体衍生病毒囊膜蛋白的分子生物学

了解杆状病毒的囊膜蛋白对揭示病毒入侵、 囊膜蛋白核定向转运机制以及研究控制昆虫新策略等方面具有重要意义。 目前研究表明,包涵体衍生病毒(occlusion-derived virus, ODV)的囊膜蛋白包括ODV-E25, ODV-E66, ODV-E56, ODV-E18, ODV-E28, P74, PIF1, PIF2, PIF3, GP41, ODV-EC27, ODV-E35, ODV-EC43,BV/ODV-E26,P91和ORF150。 本文结合国内外的研究成果系统的综述了囊膜蛋白的结构和功能,其在经口感染、调节细胞周期和囊膜蛋白的传送等方面起作用。 囊膜蛋白的核定向转运机制,ODV与昆虫中肠之间和包涵体基质之间相互作用以及ODV结构蛋白之间的相互作用等将是今后的研究重点。     

Molecular biology of Rh proteins and relevance to molecular medicine

The Rhesus (Rh) blood group system is expressed by a pair of 12-transmembrane-domain-containing proteins, the RhCcEe and RhD proteins. RhCcEe and RhD associate as a Rh core complex that comprises one RhD/CcEe protein and most likely two Rh-associated glycoproteins (RhAG) as a trimer. All these Rh proteins are homologous and share this homology with two human non-erythroid proteins, RhBG and RhCG. All Rh protein superfamily members share homology and function in a similar manner to the Mep/Amt ammonium transporters, which are highly conserved in bacteria, plants and invertebrates. Significant advances have been made in our understanding of the structure and function of Rh proteins, as well as in the clinical management of Rh haemolytic disease. This review summarises our current knowledge concerning the molecular biology of Rh proteins and their role in transfusion and pregnancy incompatibility.     

红霉素生物合成的分子生物学

近年来,国外对大环内酯类抗生素生物合成和基因工程的研究非常迅速,不仅认识了许多抗生素生物合成的过程,而且利用基因工程技术改造抗生素生物合成基因,合成了100多种非天然的“天然”抗生素。抗生素生物合成的分子生物学是抗生素基因工程的基础。本全面介绍了五厌内酯类抗生素的代表－红霉素生物合成分子生物学的历史、现状及发展趋势。     

Molecular biology of archaebacteria

In the process of phylogenetic studies, based on the comparative analysis of sequences of 16S (18S) rRNA, C. Woese and collaborators discovered that some microorganisms, which previously had been described as bacteria, form a group named archaebacteria, differing from other bacteria as well as from eukaryotes to the same extent as the latter differ from each other. A review of the work leading to that result, as well as characteristics of archaebacteria with emphasis on their biochemistry and molecular biology, is presented.     

Molecular biology of photosynthesis

Book reviews

Molecular biology of photosynthesisGovindjee, H.J. Bohnert, W. Bottomley, D.A. Bryant, J.E. Mullet, W.L. Ogren, H. Pakrasi, and C.R. Somerville (Eds.), Dordrecht: Kluwer Academic Publishers, 1989. xxvii + 815 pages. £130.00. ISBN 0-7923-0097-1     

Molecular biology of Leishmania

Leishmania is a trypanosomatid protozoa with a digenetic life cycle. Sandflies inject promastigotes, the free living form present in their salivary glands, into mammals where the parasite colonizes macrophages, transforming into intracellular amastigotes. The cycle is completed when during a blood meal the insect ingests infected macrophages, the amastigotes are released in the gut where they transform back into promastigotes. Leishmania has to adapt to the changing life conditions, from free-living forms in the poikilothermic insect vector to obligatory intracellular parasite in the homeothermic mammalian host. It also has to adapt to the acidic pH of the macrophage's phagolysosome where amastigotes multiply. The adaptative response of Leishmania includes morphological, physiological, and biochemical changes. Promastigotes can be grown in culture medium. Studies of changes taking place during adaptation have been facilitated by the establishment of in vitro conditions that allow the transformation of amastigotes into promastigotes and vice versa. The system is well suited for studying regulation of gene expression during adaptative differentiation. Some mechanisms of mRNA processing are unique to these protozoa: trans-splicing and RNA editing. Several genes that are differentially expressed in the two stages have been studied. No obvious cis regulatory motifs have been found in the DNA.     

Molecular biology of herbicides

One of the most dynamic areas of plant molecular biology is the investigation of the actions of three classes of herbicides: s-triazines (atrazine, simazine), glyphosate, and sulfonylureas (chlorsulfuron, sulfometuron methyl) (Figure 1). The results of this work are expected to provide the first significant applications of plant biotechnology: directly, in the genetic engineering of crop plants resistant to specific herbicides and, indirectly, in providing a molecular basis for the rational design of new herbicides for specific biological targets. s-Triazines affect photosynthesis by inhibiting the binding of quinones to the chloroplast membrane Q_B protein. An s-triazine resistant Q_B protein isolated from weeds in fields consistently treated with the herbicide has a serine in place of a glycine in this highly conserved protein. Glyphosate inhibits 5-enolpyruvyl-shikimate-3-phosphate synthase (EPSP synthase), an enzyme in the aromatic amino acid biosynthetic pathway. Mutagenized bacteria produce a resistant EPSP synthase with a substitution of serine for proline. Sulfonylureas inhibit the acetolactate synthase (ALS) of bacteria, yeast, and higher plants; this enzyme catalyzes the first step in the synthesis of branched chain amino acids. Resistant ALS has been found in bacteria, yeast and tobacco with a proline substituted by serine in yeast ALS. These findings provide a strong basis for developing projected plant biotechnology applications.     

Molecular biology of complement

Complementary DNA clones corresponding to most of the proteins of a major amplification and effector of immune host defenses, the complement system, have been isolated and characterized. Availability of these molecular probes has substantially increased our information about and understanding of the structure of the complement proteins and regulation of complement gene expression. Information about the proteins has led to the generation of potential pharmacological agents for the selective control of inflammation. Understanding of the regulatory mechanism has provided insights into the mechanisms accounting for the response to several cytokines including interferon-gamma, interleukin-1 and tumor necrosis factor. Finally, complement molecular genetics has been stimulated so that the basis for several complement deficiency disorders has been elucidated.     

Molecular biology of proteasomes

Eukaryotic proteasomes are unusually large proteins with a heterogeneous subunit composition and have been classified into two isoforms with apparently distinct sedimentation coefficients of 20S and 26S. The 20S proteasome is composed of a set of small subunits with molecular masses of 21–32 kDa. The 26S proteasome is a multi-molecular assembly, consisting of a central 20S proteasome and two terminal subsets of multiple subunits of 28–112 kDa attached to the central part in opposite orientations. The primary structures of all the subunits of mammalian and yeast 20S proteasomes have been deduced from the nucleotide sequences of cDNAs or genes isolated by recombinant DNA techniques. These genes constitute a unique multi-gene family encoding homologous polypeptides that have been conserved during evolution. In contrast, little is yet known about the terminal structures of the 26S proteasome, but the cDNA clonings of those of humans are currently in progress. In this review, I summarize available information of the structural features on eukaryotic 20S and 26S proteasomes which has been clarified by molecular-biological methods.     

Molecular biology of CLL

Recently, major advances have occurred in our understanding of the biology of chronic lymphocytic leukemia (CLL). CD5-positive CLL cells were once assumed to originate from immature, immunologically incompetent B lymphocytes, and to passively accumulate due to increased life time. In 1999, two research groups demonstrated that CLL, which is a morphologically uniform but clinically heterogenous disease, can be classified into two major subgroups on the basis of the mutational status of the immunoglobulin heavy chain (IgH) genes. It was also suggested that these two groups both originate from mature cells that have passed the antigen selection process. This hypothesis was confirmed by gene expression studies indicating a uniform pattern characteristic to memory cells, as well as specific B-cell receptor (BCR) structures supporting the existence of a functional antigen selection. The differences in the BCR signal transduction mechanisms may underlie the different clinical behavior in which zeta-associated tyrosine kinase (ZAP-70) may play a pivotal role, since elevated ZAP-70 expression is likely to be an unfavorable prognostic factor in CLL. The diagnostic testing for ZAP-70 expression plays an important role in the therapeutic decisions.