抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

RELION: implementation of a Bayesian approach to cryo-EM structure determination.

Microtubule nucleation is regulated by the γ-tubulin ring complex (γTuRC) and related γ-tubulin complexes, providing spatial and temporal control over the initiation of microtubule growth. Recent structural work has shed light on the mechanism of γTuRC-based microtubule nucleation, confirming the long-standing hypothesis that the γTuRC functions as a microtubule template. The first crystallographic analysis of a non-γ-tubulin γTuRC component (γ-tubulin complex protein 4 (GCP4)) has resulted in a new appreciation of the relationships among all γTuRC proteins, leading to a refined model of their organization and function. The structures have also suggested an unexpected mechanism for regulating γTuRC activity via conformational modulation of the complex component GCP3. New experiments on γTuRC localization extend these insights, suggesting a direct link between its attachment at specific cellular sites and its activation.

Microtubule nucleation by γ-tubulin complexes

Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets

The Spliceosome: Design Principles of a Dynamic RNP Machine

The crystal structure of the bacterial 70S ribosome refined to 2.8 angstrom resolution reveals atomic details of its interactions with messenger RNA (mRNA) and transfer RNA (tRNA). A metal ion stabilizes a kink in the mRNA that demarcates the boundary between A and P sites, which is potentially important to prevent slippage of mRNA. Metal ions also stabilize the intersubunit interface. The interactions of E-site tRNA with the 50S subunit have both similarities and differences compared to those in the archaeal ribosome. The structure also rationalizes much biochemical and genetic data on translation.

https://science.sciencemag.org/content/sci/313/5795/1935.full.pdf

Structure of the 70S Ribosome Complexed with mRNA and tRNA

http://zhiyuan.sjtu.edu.cn/file/course/20131129095824_Ma%20Le-Discussion(Dec.3).pdf

Branching Microtubule Nucleation in Xenopus Egg Extracts Mediated by Augmin and TPX2

The termination of protein synthesis occurs through the specific recognition of a stop codon in the A site of the ribosome by a release factor (RF), which then catalyzes the hydrolysis of the nascent protein chain from the P-site transfer RNA. Here we present, at a resolution of 3.5 angstroms, the crystal structure of RF2 in complex with its cognate UGA stop codon in the 70S ribosome. The structure provides insight into how RF2 specifically recognizes the stop codon; it also suggests a model for the role of a universally conserved GGQ motif in the catalysis of peptide release.

/pdf/insights-into-translational-termination-from-the-structure-545o1e5zmg.pdf

Insights into Translational Termination from the Structure of RF2 Bound to the Ribosome

http://www.biochem.emory.edu/dunham/documents/Petry%20et%20al.,%20Cell%202005.pdf

Crystal structures of the ribosome in complex with release factors RF1 and RF2 bound to a cognate stop codon.

The mitotic spindle is constructed from microtubules (MTs) nucleated from centrosomes, chromosome proximal regions, and preexisting spindle MTs. Augmin, a recently identified protein complex, is a critical factor in spindle MT-based MT generation in Drosophila S2 cells. Previously, we identified one subunit of human augmin. Here, by using mass spectrometry, we identified the full human augmin complex of 8 subunits and show that it interacts with the γ-tubulin ring complex (γ-TuRC). Unlike augmin-depleted S2 cells, in which the defect in spindle-mediated MT generation is mostly compensated by centrosomal MTs, augmin knockdown alone in HeLa cells triggers the spindle checkpoint, reduces tension on sister kinetochores, and severely impairs metaphase progression. Human augmin knockdown also reduces the number of central spindle MTs during anaphase and causes late-stage cytokinesis failure. A link between augmin and γ-TuRC is likely critical for these functions, because a γ-TuRC mutant that attenuates interaction with augmin does not restore function in vivo. These results demonstrate that MT generation mediated by augmin and γ-TuRC is critical for chromosome segregation and cytokinesis in human cells.

https://www.pnas.org/content/pnas/106/17/6998.full.pdf

Sabine Petry

Papers

Structure of the 70S Ribosome Complexed with mRNA and tRNA

Branching Microtubule Nucleation in Xenopus Egg Extracts Mediated by Augmin and TPX2

Insights into Translational Termination from the Structure of RF2 Bound to the Ribosome

Crystal structures of the ribosome in complex with release factors RF1 and RF2 bound to a cognate stop codon.

The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells