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

Views of how cell membranes are organized are presently changing. The lipid bilayer that constitutes these membranes is no longer understood to be a homogeneous fluid. Instead, lipid assemblies, termed rafts, have been introduced to provide fluid platforms that segregate membrane components and dynamically compartmentalize membranes. These assemblies are thought to be composed mainly of sphingolipids and cholesterol in the outer leaflet, somehow connected to domains of unknown composition in the inner leaflet. Specific classes of proteins are associated with the rafts. This review critically analyzes what is known of phase behavior and liquid-liquid immiscibility in model systems and compares these data with what is known of domain formation in cell membranes.

/pdf/model-systems-lipid-rafts-and-cell-membranes-23ceb2z39h.pdf

Model systems, lipid rafts, and cell membranes.

http://www4.utsouthwestern.edu/moleculargenetics/pdf/msb_cur_res/2006%20CELL%20Goldstein%2035.pdf

Protein Sensors for Membrane Sterols

https://www.cell.com/biophysj/pdf/S0006-3495(03)74726-2.pdf

Separation of liquid phases in giant vesicles of ternary mixtures of phospholipids and cholesterol.

▪ Abstract Lipid raft microdomains were conceived as part of a mechanism for the intracellular trafficking of lipids and lipid-anchored proteins. The raft hypothesis is based on the behavior of defined lipid mixtures in liposomes and other model membranes. Experiments in these well-characterized systems led to operational definitions for lipid rafts in cell membranes. These definitions, detergent solubility to define components of rafts, and sensitivity to cholesterol deprivation to define raft functions implicated sphingolipid- and cholesterol-rich lipid rafts in many cell functions. Despite extensive work, the basis for raft formation in cell membranes and the size of rafts and their stability are all uncertain. Recent work converges on very small rafts <10 nm in diameter that may enlarge and stabilize when their constituents are cross-linked.

https://www.physics.iitm.ac.in/~iol/lecture_notes/vani/general-lipid-stuff/lipid-rafts-2003-ann.rev.pdf

The state of lipid rafts: from model membranes to cells.

Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor proteins called Insigs. Here, we show that oxysterols act by binding to Insigs, causing Insigs to bind to Scap. Mutational analysis of the six transmembrane helices of Insigs reveals that the third and fourth are important for Insig's binding to oxysterols and to Scap. These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells.

https://www.pnas.org/content/pnas/104/16/6511.full.pdf

Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig.

Switch-like Control of SREBP-2 Transport Triggered by Small Changes in ER Cholesterol: A Delicate Balance

Egress of lipoprotein-derived cholesterol from lysosomes requires two lysosomal proteins, polytopic membrane-bound Niemann–Pick C1 (NPC1) and soluble Niemann–Pick C2 (NPC2). The reason for this dual requirement is unknown. Previously, we showed that the soluble luminal N-terminal domain (NTD) of NPC1 (amino acids 25–264) binds cholesterol. This NTD is designated NPC1(NTD). We and others showed that soluble NPC2 also binds cholesterol. Here, we establish an in vitro assay to measure transfer of [3H]cholesterol between these two proteins and phosphatidylcholine liposomes. Whereas NPC2 rapidly donates or accepts cholesterol from liposomes, NPC1(NTD) acts much more slowly. Bidirectional transfer of cholesterol between NPC1(NTD) and liposomes is accelerated >100-fold by NPC2. A naturally occurring human mutant of NPC2 (Pro120Ser) fails to bind cholesterol and fails to stimulate cholesterol transfer from NPC1(NTD) to liposomes. NPC2 may be essential to deliver or remove cholesterol from NPC1, an interaction that links both proteins to the cholesterol egress process from lysosomes. These findings may explain how mutations in either protein can produce a similar clinical phenotype.

https://www.pnas.org/content/pnas/105/40/15287.full.pdf

NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes

https://www.cell.com/biophysj/pdf/S0006-3495(99)76998-5.pdf

Arun Radhakrishnan

Papers

Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig.

Switch-like Control of SREBP-2 Transport Triggered by Small Changes in ER Cholesterol: A Delicate Balance

NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes

Condensed complexes of cholesterol and phospholipids

Condensed complexes of cholesterol and phospholipids.