近日,，美國新澤西州大學(xué)研究人員發(fā)現(xiàn)心肌病作為一種隱襲疾病,，通常會在沒有任何前兆的情況下發(fā)作，進而導(dǎo)致心力衰竭并最終致死,。心肌病能追蹤高血壓,、心瓣膜或動脈疾病以及先天性心臟缺損等疾病，它也是由血液中的病毒感染所致,。
研究結(jié)果發(fā)表在7月出版的《自然結(jié)構(gòu)和分子生物學(xué)》雜志中,，研究人員發(fā)現(xiàn)了一種重要動力蛋白的可能作用機制，這種蛋白有點像催化劑,，它可使體外的細菌通過血液感染到器官如心臟,。
心肌病的發(fā)病主要是由動力蛋白SecA的解螺旋酶引起，發(fā)現(xiàn)這種動力蛋白作用途徑的意義是重大的,，因為可以因此產(chǎn)生新的藥理學(xué)治療方法,，可靶向并殺死細菌，進而預(yù)防或減小對心肌的損傷,。
利用高分辨率核磁共振分光術(shù),，研究人員發(fā)現(xiàn)了動力蛋白SecA的功能機制，SecA可將化學(xué)能轉(zhuǎn)化為機械能,。目前僅僅在細菌中發(fā)現(xiàn)了SecA,，人類還沒有這種蛋白，SecA可通過使用機械能來將毒素和其它有害蛋白分泌到細菌細胞外部,。
細菌感染人類或宿主后,，它們通過SecA系統(tǒng)來“掩護”特殊的細菌蛋白侵入人體進而引起感染或疾病。隨著高分辨率核磁共振分光術(shù)的應(yīng)用,，研究人員可以觀察到蛋白質(zhì)在運動中的作用情況,。核磁共振分光術(shù)是通過利用物質(zhì)發(fā)出的無線電波間產(chǎn)生的一種交互作用為研究人員提供一個詳細的動態(tài)圖片，而不同于其它技術(shù)如X射線衍射晶體分析法提供的靜態(tài)顯像,。
研究人員將這種動力蛋白和發(fā)現(xiàn)的細菌活性比喻為人們常常會接觸到的郵寄和投遞信件的郵政編碼系統(tǒng),。細菌一旦感染了宿主或人，這種細菌就會用SecA來閱讀“郵政編碼”系統(tǒng)以“掩護”特定的細菌蛋白進入人體,。
這些蛋白是如何隱瞞人體系統(tǒng)的還不得而知,，它在某些情況下還可能引起卒中和心力衰竭。在了解這些蛋白的作用途徑之后,，研究人員便可研制出新的藥物,，抑制這些蛋白質(zhì)分泌或限制SecA活性，進而在細菌在到達目的地之前殺死它,。
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."
