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

https://www.cell.com/cell/pdf/S0092-8674(03)00759-1.pdf

Asymmetry in the assembly of the RNAi enzyme complex.

The structure

Helicases and translocases are a ubiquitous, highly diverse group of proteins that perform an extraordinary variety of functions in cells. Consequently, this review sets out to define a nomenclature for these enzymes based on current knowledge of sequence, structure, and mechanism. Using previous definitions of helicase families as a basis, we delineate six superfamilies of enzymes, with examples of crystal structures where available, and discuss these structures in the context of biochemical data to outline our present understanding of helicase and translocase activity. As a result, each superfamily is subdivided, where appropriate, on the basis of mechanistic understanding, which we hope will provide a framework for classification of new superfamily members as they are discovered and characterized.

Structure and mechanism of helicases and nucleic acid translocases.

https://zenodo.org/record/1229904/files/article.pdf

Classification and evolution of P-loop GTPases and related ATPases.

http://mcb.berkeley.edu/courses/mcb110/210X/2-Velankar-helicase.pdf

Crystal structures of complexes of PcrA DNA helicase with a DNA substrate indicate an inchworm mechanism.

Head-on encounters between the replication and transcription machineries on the lagging DNA strand can lead to replication fork arrest and genomic instability. To avoid head-on encounters, most genes, especially essential and highly transcribed genes, are encoded on the leading strand such that transcription and replication are co-directional. Virtually all bacteria have the highly expressed ribosomal RNA genes co-directional with replication. In bacteria, co-directional encounters seem inevitable because the rate of replication is about 10-20-fold greater than the rate of transcription. However, these encounters are generally thought to be benign. Biochemical analyses indicate that head-on encounters are more deleterious than co-directional encounters and that in both situations, replication resumes without the need for any auxiliary restart proteins, at least in vitro. Here we show that in vivo, co-directional transcription can disrupt replication, leading to the involvement of replication restart proteins. We found that highly transcribed rRNA genes are hotspots for co-directional conflicts between replication and transcription in rapidly growing Bacillus subtilis cells. We observed a transcription-dependent increase in association of the replicative helicase and replication restart proteins where head-on and co-directional conflicts occur. Our results indicate that there are co-directional conflicts between replication and transcription in vivo. Furthermore, in contrast to the findings in vitro, the replication restart machinery is involved in vivo in resolving potentially deleterious encounters due to head-on and co-directional conflicts. These conflicts probably occur in many organisms and at many chromosomal locations and help to explain the presence of important auxiliary proteins involved in replication restart and in helping to clear a path along the DNA for the replisome.

Co-directional replication–transcription conflicts lead to replication restart

DNA footprinting and nuclease protection studies of PcrA helicase complexed with a 3′-tailed DNA duplex reveal a contact region that covers a significant region of the substrate both in the presence and absence of a non-hydrolysable analogue of ATP, ADPNP However, details of the interactions of the enzyme with the duplex region are altered upon binding of nucleotide By combining this information with that obtained from crystal structures of PcrA complexed with a similar DNA substrate, we have designed mutant proteins that are defective in helicase activity but that leave the ATPase and single-stranded DNA translocation activities intact These mutants are all located in domains 1B and 2B, which interact with the duplex portion of the DNA substrate Taken together with the crystal structures, these data support an ‘active’ mechanism for PcrA that involves two distinct ATP-dependent processes: destabilization of the duplex DNA ahead of the enzyme that is coupled to DNA translocation along the single strand product

/pdf/uncoupling-dna-translocation-and-helicase-activity-in-pcra-g6oznozk97.pdf

Panos Soultanas

Papers

Crystal structures of complexes of PcrA DNA helicase with a DNA substrate indicate an inchworm mechanism.

Co-directional replication–transcription conflicts lead to replication restart

Uncoupling DNA translocation and helicase activity in PcrA: direct evidence for an active mechanism.

Unwinding the ‘Gordian knot’ of helicase action

DNA binding mediates conformational changes and metal ion coordination in the active site of PcrA helicase