近日，美国新泽西州大学研究人员发现心肌病作为一种隐袭疾病，通常会在没有任何前兆的情况下发作，进而导致心力衰竭并最终致死。心肌病能追踪高血压、心瓣膜或动脉疾病以及先天性心脏缺损等疾病，它也是由血液中的病毒感染所致。
研究结果发表在7月出版的《自然结构和分子生物学》杂志中，研究人员发现了一种重要动力蛋白的可能作用机制，这种蛋白有点像催化剂，它可使体外的细菌通过血液感染到器官如心脏。
心肌病的发病主要是由动力蛋白SecA的解螺旋酶引起，发现这种动力蛋白作用途径的意义是重大的，因为可以因此产生新的药理学治疗方法，可靶向并杀死细菌，进而预防或减小对心肌的损伤。
利用高分辨率核磁共振分光术，研究人员发现了动力蛋白SecA的功能机制，SecA可将化学能转化为机械能。目前仅仅在细菌中发现了SecA，人类还没有这种蛋白，SecA可通过使用机械能来将毒素和其它有害蛋白分泌到细菌细胞外部。
细菌感染人类或宿主后，它们通过SecA系统来“掩护”特殊的细菌蛋白侵入人体进而引起感染或疾病。随着高分辨率核磁共振分光术的应用，研究人员可以观察到蛋白质在运动中的作用情况。核磁共振分光术是通过利用物质发出的无线电波间产生的一种交互作用为研究人员提供一个详细的动态图片，而不同于其它技术如X射线衍射晶体分析法提供的静态显像。
研究人员将这种动力蛋白和发现的细菌活性比喻为人们常常会接触到的邮寄和投递信件的邮政编码系统。细菌一旦感染了宿主或人，这种细菌就会用SecA来阅读“邮政编码”系统以“掩护”特定的细菌蛋白进入人体。
这些蛋白是如何隐瞒人体系统的还不得而知，它在某些情况下还可能引起卒中和心力衰竭。在了解这些蛋白的作用途径之后，研究人员便可研制出新的药物，抑制这些蛋白质分泌或限制SecA活性，进而在细菌在到达目的地之前杀死它。
英文原文：
Motor protein SecA linked to Cardiomyopathy
By Rutgers, the State University of New Jersey, Cardiomyopathy is an insidious disease which often strikes without warning and can lead to heart failure and eventual death. Although the disease can be traced to conditions such as high blood pressure, heart valve or arterial diseases and congenital heart defects, it is also caused by viral infections in the bloodstream. In a paper to be published in the July issue of the journal Nature Structural and Molecular Biology, a Rutgers-Newark researcher and his coworkers reveal that they have identified a possible mechanism used by an important motor protein which acts as a catalyst that enables bacteria outside the human body to travel through the blood stream and infect organs such as the heart.
The findings were published by Rutgers-Newark Chemistry Assistant Professor Charalampos Kalodimos and his coworkers, in the article, "Disorder-order folding transitions underlie catalysis in the helicase motor of SecA." Identifying the way this motor protein works is significant because it may lead to the development of new pharmacological therapies which can target and kill the bacteria to prevent or minimize damage to the heart muscle. The results follow nearly two years of research funded by a $300,000 American Heart Association (AHA) grant. The AHA agreed to support Kalodimos's research because he is focusing on specific bacteria that cause cardiovascular diseases in both adults and children.
Using high-resolution NMR Spectroscopy technology, Kalodimos identified the mechanism of function of motor protein SecA, which uses chemical energy and converts it into mechanical energy. SecA is present only in bacteria and is not found in humans. SecA uses mechanical energy to secrete toxins and other harmful proteins to the exterior of the bacterium cell.
Once a bacterium infects a human or a host, some bacteria will use the SecA system to secrete specific bacteria proteins into the human body causing infections or diseases. Recent advances in NMR Spectroscopy allowed Kalodimos and his coworkers to observe how proteins work in motion. NMR spectroscopy exploits the interaction of radio waves with matter to give scientists a moving picture of molecular structures within the body. The methodology used in Kalodimos group provides researchers with detailed, moving pictures rather than static images produced by other technologies such as X-ray crystallography. Kalodimos likens the motor protein and bacteria activity he has identified to the United State Postal Service's zip code system used to process mail and direct it to its final destination.
"A city as a large as New York City has several different zip codes and a central post office must be present to scan and read these zip codes so the letters can reach their intended destinations," Kalodimos explains. "Proteins have one signal that operates similar to a zip code. The protein "zip code" is read or scanned by some specific protein or large protein machineries. These machineries are needed to transport the protein to the correct compartment within a cell."
He explained that once a bacterium infects a host or human, certain bacteria will use SecA to read the "zip code" system to secrete specific bacteria proteins into the human body.
"Somehow they fool the human body that these are human proteins and the human body begins to use them which may cause a stroke or heart failure in some cases," Kalodimos explains. "By identifying the way this motor protein works, at some point we will be able to develop drugs that can block the secretion of these proteins or limit the activity of SecA causing the bacteria to die before it can reach its destination."
