HIV-1蛋白酶是病毒成熟所不可或缺的，这使其成为抗HIV疗法的一大潜在目标。它所起作用是将新形成的聚合蛋白质Gag 和 Gag-Pol分开，以产生结构和功能蛋白的成品，包括其本身在内。现在，研究人员利用NMR光谱和“顺磁弛豫增强”对HIV-1蛋白酶自处理过程中的早期事件（在这些事件中，一个前体二聚物被认为经历分子内解理）进行了观察。
该研究显示，虽然这种蛋白酶主要是单体的，但它也以瞬时“遭遇络合物”（encounter complexes）的形式存在，这些络合物相对于成熟二聚物有一系列不同取向。N-端区域与基质结合点发生瞬时亚单元内和亚单元间接触，使得当“遭遇络合物”处于正确二聚物取向时自解理能够发生。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 455, 693-696 (2 October 2008) | doi:10.1038/nature07342
Visualizing transient events in amino-terminal autoprocessing of HIV-1 protease
Chun Tang, John M. Louis1, Annie Aniana, Jeong-Yong Suh & G. Marius Clore
HIV-1 protease processes the Gag and Gag-Pol polyproteins into mature structural and functional proteins, including itself, and is therefore indispensable for viral maturation1, 2. The mature protease is active only as a dimer3, 4, 5 with each subunit contributing catalytic residues6. The full-length transframe region protease precursor appears to be monomeric yet undergoes maturation via intramolecular cleavage of a putative precursor dimer5, 7, 8, 9, 10, 11, concomitant with the appearance of mature-like catalytic activity7, 9. How such intramolecular cleavage can occur when the amino and carboxy termini of the mature protease are part of an intersubunit -sheet located distal from the active site is unclear. Here we visualize the early events in N-terminal autoprocessing using an inactive mini-precursor with a four-residue N-terminal extension that mimics the transframe region protease precursor5, 12. Using paramagnetic relaxation enhancement, a technique that is exquisitely sensitive to the presence of minor species13, 14, 15, 16, we show that the mini-precursor forms highly transient, lowly populated (3–5%) dimeric encounter complexes that involve the mature dimer interface but occupy a wide range of subunit orientations relative to the mature dimer. Furthermore, the occupancy of the mature dimer configuration constitutes a very small fraction of the self-associated species (accounting for the very low enzymatic activity of the protease precursor), and the N-terminal extension makes transient intra- and intersubunit contacts with the substrate binding site and is therefore available for autocleavage when the correct dimer orientation is sampled within the encounter complex ensemble.
