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

J. Appl. Cryst.の発刊に際して

Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy.

Structure of lipid bilayers

https://www.embl-hamburg.de/biosaxs/reprints/dammin_1999.pdf

Restoring low resolution structure of biological macromolecules from solution scattering using simulated annealing.

The structure of the protein–solvent interface is the subject of controversy in theoretical studies and requires direct experimental characterization. Three proteins with known atomic resolution crystal structure (lysozyme, Escherichia coli thioredoxin reductase, and protein R1 of E. coli ribonucleotide reductase) were investigated in parallel by x-ray and neutron scattering in H2O and D2O solutions. The analysis of the protein–solvent interface is based on the significantly different contrasts for the protein and for the hydration shell. The results point to the existence of a first hydration shell with an average density ≈10% larger than that of the bulk solvent in the conditions studied. Comparisons with the results of other studies suggest that this may be a general property of aqueous interfaces.

https://www.embl-hamburg.de/biosaxs/reprints/cryson_1998.pdf

Protein hydration in solution: Experimental observation by x-ray and neutron scattering

An effective environmental force constant is introduced to quantify the molecular resilience (or its opposite, “softness”) of a protein structure and relate it to biological function and activity. Specific resilience-function relations were found in neutron-scattering experiments on purple membranes containing bacteriorhodopsin, the light-activated proton pump of halobacteria; the connection between resilience and stability is illustrated by a study of myoglobin in different environments. Important advantages of the neutron method are that it can characterize the dynamics of any type of biological sample—which need not be crystalline or monodisperse—and that it enables researchers to focus on the dynamics of specific parts of a complex structure with deuterium labeling.

/pdf/how-soft-is-a-protein-a-protein-dynamics-force-constant-4ldrmeu5nn.pdf

How Soft Is a Protein? A Protein Dynamics Force Constant Measured by Neutron Scattering

It is now clear that the understanding of halophilic adaptation at a molecular level requires a strategy of complementary experiments, combining molecular biology, biochemistry, and cellular approaches with physical chemistry and thermodynamics. In this review, after a discussion of the definition and composition of halophilic enzymes, the effects of salt on their activity, solubility, and stability are reviewed. We then describe how thermodynamic observations, such as parameters pertaining to solvent-protein interactions or enzyme-unfolding kinetics, depend strongly on solvent composition and reveal the important role played by water and ion binding to halophilic proteins. The three high-resolution crystal structures now available for halophilic proteins are analyzed in terms of haloadaptation, and finally cellular response to salt stress is discussed briefly.

Halophilic adaptation of enzymes.

NEUTRON diffraction combined with the use of selectively deuterated lipids can provide detailed information on the molecular structure of membranes. Because of the large difference between the coherent scattering length of hydrogen ( −3.74 fermis) and deuterium (6.67 fermis) the deuterated membrane segments show up as intense peaks in the neutron density profile and can thus easily be located in the membrane1–3. We have applied this method to bilayer membranes of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), selectively deuterated at 12 different positions in the polar head group and the hydrocarbon chains. We report here that the mean position of the deuterated segments within the membrane can be determined in most cases to a precision of better than ±1 A. The average orientation of the phosphocholine group in the gel state as well as in the liquid crystalline state is almost parallel to the membrane surface. In the gel state the two hydrocarbon chains are out of step by about 1.8 A, and water penetrates up to the glycerol backbone of the lipid molecules.

Neutron diffraction studies on selectively deuterated phospholipid bilayers

The internal dynamics of bacteriorhodopsin, the light-driven proton pump in the purple membrane of Halobacterium halobium, has been studied by inelastic neutron scattering for various conditions of temperature and hydration. Light activation can take place when the membrane is vibrating harmonically. The ability of the protein to functionally relax and complete the photocycle initiated by the absorption of a photon, however, is strongly correlated with the onset of low-frequency, large-amplitude anharmonic atomic motions in the membrane. For a normally hydrated sample, this occurs at about 230 K, where a dynamical transition from a low-temperature harmonic regime is observed. In moderately dry samples, on the other hand, in which the photocycle is slowed down by several orders of magnitude, no transition is observed and protein motions remain approximately harmonic up to room temperature. These results support the hypothesis, made from previous neutron diffraction studies, that the "softness" of the membrane modulates the function of bacteriorhodopsin by allowing or not allowing large-amplitude motions in the protein.

Giuseppe Zaccai

Papers

Protein hydration in solution: Experimental observation by x-ray and neutron scattering

How Soft Is a Protein? A Protein Dynamics Force Constant Measured by Neutron Scattering

Halophilic adaptation of enzymes.

Neutron diffraction studies on selectively deuterated phospholipid bilayers

Thermal motions and function of bacteriorhodopsin in purple membranes: effects of temperature and hydration studied by neutron scattering