Improving transmembrane protein consensus topology prediction using inter-helical interaction

Alpha helix transmembrane proteins (αTMPs) represent roughly 30% of all open reading frames (ORFs) in a typical genome and are involved in many critical biological processes. Due to the special physicochemical properties, it is hard to crystallize and obtain high resolution structures experimentally, thus, sequence-based topology prediction is highly desirable for the study of transmembrane proteins (TMPs), both in structure prediction and function prediction. Various model-based topology prediction methods have been developed, but the accuracy of those individual predictors remain poor due to the limitation of the methods or the features they used. Thus, the consensus topology prediction method becomes practical for high accuracy applications by combining the advances of the individual predictors. Here, based on the observation that inter-helical interactions are commonly found within the transmembrane helixes (TMHs) and strongly indicate the existence of them, we present a novel consensus topology prediction method for αTMPs, CNTOP, which incorporates four top leading individual topology predictors, and further improves the prediction accuracy by using the predicted inter-helical interactions. The method achieved 87% prediction accuracy based on a benchmark dataset and 78% accuracy based on a non-redundant dataset which is composed of polytopic αTMPs. Our method derives the highest topology accuracy than any other individual predictors and consensus predictors, at the same time, the TMHs are more accurately predicted in their length and locations, where both the false positives (FPs) and the false negatives (FNs) decreased dramatically. The CNTOP is available at: http://ccst.jlu.edu.cn/JCSB/cntop/CNTOP.html.     

A novel carbonyl reductase from Pichia stipitis for the production of ethyl (S)-4-chloro-3-hydroxybutanoate

An NADPH-dependent carbonyl reductase (PsCR) gene from Pichia stipitis was cloned. It contains an open reading frame of 849 bp encoding 283 amino acids whose sequence had less than 60% identity to known reductases that produce ethyl (S)-4-chloro-3-hydroxybutanoates (S-CHBE). When expressed in Escherichia coli, the recombinant PsCR exhibited an activity of 27 U/mg using ethyl 4-chloro-3-oxobutanoate (COBE) as a substrate. Reduction of COBE to (S)-CHBE by transformants in an aqueous mono-phase system for 18 h, gave a molar yield of 94% and an optical purity of the (S)-isomer of more than 99% enantiomeric excess.     

The crystal structure of BlmI as a model for nonribosomal peptide synthetase peptidyl carrier proteins

Carrier proteins (CPs) play a critical role in the biosynthesis of various natural products, especially in nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzymology, where the CPs are referred to as peptidyl‐carrier proteins (PCPs) or acyl‐carrier proteins (ACPs), respectively. CPs can either be a domain in large multifunctional polypeptides or standalone proteins, termed Type I and Type II, respectively. There have been many biochemical studies of the Type I PKS and NRPS CPs, and of Type II ACPs. However, recently a number of Type II PCPs have been found and biochemically characterized. In order to understand the possible interaction surfaces for combinatorial biosynthetic efforts we crystallized the first characterized and representative Type II PCP member, BlmI, from the bleomycin biosynthetic pathway from Streptomyces verticillus ATCC 15003. The structure is similar to CPs in general but most closely resembles PCPs. Comparisons with previously determined PCP structures in complex with catalytic domains reveals a common interaction surface. This surface is highly variable in charge and shape, which likely confers specificity for interactions. Previous nuclear magnetic resonance (NMR) analysis of a prototypical Type I PCP excised from the multimodular context revealed three conformational states. Comparison of the states with the structure of BlmI and other PCPs reveals that only one of the NMR states is found in other studies, suggesting the other two states may not be relevant. The state represented by the BlmI crystal structure can therefore serve as a model for both Type I and Type II PCPs. Proteins 2014; 82:1210–1218. © 2013 Wiley Periodicals, Inc.     

黄猄蚁对橡胶盔蚧种群消长的影响

调查西双版纳地区黄猄蚁OecophyllasmaragdinaFabricius对橡胶盔蚧Parasaissetianigra(Nietner)种群数量和寄生蜂的影响。结果表明:黄猄蚁对橡胶盔蚧种群消长及寄生蜂均有影响。"有蚂蚁"枝条上介壳虫种群数量显著高于"无蚂蚁"枝条。"有蚂蚁"枝条介壳虫死亡率和寄生蜂都显著低于"无蚂蚁"枝条。说明黄猄蚁的存在影响了橡胶树介壳虫的种群繁殖率和死亡率。建议在今后综合防治中,充分利用蚂蚁与橡胶树介壳虫关系。通过驱逐橡胶树上的蚂蚁来有效遏制介壳虫的发生。     

孕期应激对子代大鼠骨髓淋巴干细胞发育的影响

孕期应激对子代产生的影响是多方面的,这种影响是复杂的。研究表明,出生前的应激经历可导致出生后子代长期的免疫功能改变。这些改变追其根源与骨髓淋巴干细胞的改变有关。本文综述了大鼠孕期经历应激的子代骨髓淋巴干细胞所受的影响及免疫系统的相关改变,并根据现有的研究提出假说,为进一步研究孕期应激导致子代免疫系统改变的机理研究提供新的思路。     

Bone morphogenetic protein-4

Bone morphogenetic protein-4 (BMP-4) is one of nine structurally related BMPs belonging to the transforming growth factor-β (TGF-β) superfamily of secreted proteins. Mature BMP-4 is a dimer that binds to a multimeric transmembrane receptor with serine/threonine kinase activity. Although discovered because it stimulates bone formation in adult mammals, BMP-4 has important roles as a signalling molecule in embryonic tissues, including the developing central and peripheral nervous system, musculature and skeleton. It participates in an ancient signalling pathway also found in insects and worms. Nevertheless, the main practical application of BMPs is for stimulating repair of bone, and their use in humans is currently being assessed.