HIV-1蛋白酶是病毒成熟所不可或缺的,，這使其成為抗HIV療法的一大潛在目標(biāo),。它所起作用是將新形成的聚合蛋白質(zhì)Gag 和 Gag-Pol分開,，以產(chǎn)生結(jié)構(gòu)和功能蛋白的成品,，包括其本身在內(nèi)?，F(xiàn)在,，研究人員利用NMR光譜和“順磁弛豫增強(qiáng)”對HIV-1蛋白酶自處理過程中的早期事件（在這些事件中,，一個前體二聚物被認(rèn)為經(jīng)歷分子內(nèi)解理）進(jìn)行了觀察,。
該研究顯示，雖然這種蛋白酶主要是單體的,，但它也以瞬時“遭遇絡(luò)合物”（encounter complexes）的形式存在,，這些絡(luò)合物相對于成熟二聚物有一系列不同取向。N-端區(qū)域與基質(zhì)結(jié)合點(diǎn)發(fā)生瞬時亞單元內(nèi)和亞單元間接觸,，使得當(dāng)“遭遇絡(luò)合物”處于正確二聚物取向時自解理能夠發(fā)生,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
