研究：原子状态下观测艾滋病诱因

Since the discovery in 2007 that a component（组件，成分） of human semen（精液） called SEVI boosts infectivity（传染性） of the virus that causes AIDS, researchers have been trying to learn more about SEVI and how it works, in hopes of thwarting（阻遏，反对） its infection-promoting activity. Now, scientists at the University of Michigan have determined the atomic-level, three-dimensional structure of a SEVI precursor（先驱者，前导） known as PAP248-286 and discovered how it damages cell membranes（细胞膜） to make them more vulnerable to（易受……的攻击） infection with HIV. The work is described in two new papers. The most recent, describing the structure, was published online Nov. 17 in the Journal of the American Chemical Society. The paper describing how PAP248-286 interacts with cell membranes appeared in the Nov. 4 issue of Biophysical Journal.

PAP248-286 is a peptide（肽）---a chain of amino acids（氨基酸） not long enough to be considered a protein. Individual PAP248-286 peptides have a tendency to clump together to form amyloid（淀粉质的） fibers called SEVI (semen enhancer of viral infection). Amyloid fibers are of great interest because they are the calling cards of many neurodegenerative diseases（神经退行性疾病，老年痴呆症）, such as Alzheimer's and Parkinson's, and aging-related diseases like type-2 diabetes（糖尿病）. Using NMR (nuclear magnetic resonance核磁共振) spectroscopy（光谱学）, a technique that not only yields atomic-level details of a molecule's structure, but also shows how the molecule nestles（挨靠，安置） into the membrane with which it interacts, researcher Ayyalusamy Ramamoorthy and coworkers found that the structure of PAP248-286 is unlike that of most other amyloid-forming peptides and proteins.

In solution, SEVI is completely unstructured or has no definite shape and is therefore ineffective. On the other hand, "when bound to the membrane, it's in a spaghetti（意大利式细面条）-like arrangement---a disorganized, loose coil（松卷，松开的蛋卷）," said Ramamoorthy, a professor of chemistry and of biophysics（生物物理学）. In contrast, most other amyloid proteins assume a more ordered, helical configuration（螺旋构型）. Also unlike other amyloid peptides, SEVI does not penetrate deep into the greasy（油腻的，泥泞的） region of the cell membrane（薄膜，羊皮纸）, but is located near the surface. Ramamoorthy and coauthors believe the spread-out, disordered configuration and its location in the cell membrane may explain the ability of SEVI fibers to enhance HIV infection, as the arrangement provides more surface area with which the virus can interact.

A key finding of the second study is that PAP248-286 "shocks" the membrane, inducing a structural change---a kind of dimple（酒窝，涟漪） that allows HIV to attach to and enter the cell.

Next, Ramamoorthy and colleagues hope to discern more structural details of PAP248-286 and SEVI. They also plan to screen antioxidant（抗氧化剂） compounds such as green tea extract, curcumin（姜黄素） and resveratrol（白藜芦醇） (found in red wine) to see if such compounds are capable of blocking SEVI's HIV-enhancing activity.