A single deletion at position 134, 135, or 136 in the beta 7-beta 8 loop of the p51 subunit of HIV-1 RT disrupts the formation of heterodimeric enzyme.
A single deletion at position 134, 135, or 136 in the beta 7-beta 8 loop of the p51 subunit of HIV-1 RT disrupts the formation of heterodimeric enzyme.
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HIV-1 RT p51 亚基的 β7-β8 环中第 134、135 或 136 位的单个缺失会破坏异二聚酶的形成。
DOI：
10.1002/jcb.22439
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发表时间：
2010
影响因子：
4
通讯作者：
Pandey,VirendraN
中科院分区：
文献类型：
--
作者：
Upadhyay,Alok;Pandey,Nootan;Mishra,ChaturbhujA;Talele,TanajiT;Pandey,VirendraN
人类免疫缺陷病毒1型逆转录酶（HIV-1 RT）是由p66和p51亚基组成的异二聚体酶。早些时候，我们表明p51的b7-b8环对于HIV-1 RT的聚合酶活性是至关重要的，因为p51亚基中跨越残基136-139的b7-b8环中氨基酸的缺失或Ala取代损害了二聚化，进而损害了酶的聚合酶功能（Pandey et al. [2001] Biochemistry 40：9505-9512）。在本研究中，我们在位置134，135，136或137处产生了亚基特异性单缺失突变体，并研究了它们对酶的异源二聚化，二元复合物形成和聚合酶功能的影响。我们发现，在这四个残基中，Ser 134，Ile 135和Asn 136在p51亚基的b7-b8环中是酶的二聚化和聚合酶功能的关键残基，但当从p66亚基特异性删除时没有影响。这些结果表明p51亚基的b7-b8环在形成稳定的功能性异源二聚体酶中可能是抗HIV-1药物开发的有吸引力的靶点。J.细胞。© 2009 Wiley-Liss，Inc.
The human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a heterodimeric enzyme composed of p66 and p51 subunits. Earlier, we showed that the b7–b8 loop of p51 is crucial for polymerase activity of HIV-1 RT as either deletion or Ala substitution of amino acids in the b7–b8 loop spanning residues 136-139 in the p51 subunit impaired dimerization and, in turn, polymerase function of the enzyme (Pandey et al.[2001] Biochemistry 40: 9505–9512). In the present study, we generated subunit-specific single-deletion mutants at positions 134, 135, 136, or 137 and examined their effects on the heterodimerization, binary complex formation, and polymerase functions of the enzyme. We found that among these four residues, Ser134, Ile135, and Asn136 in the b7–b8 loop of the p51 subunit are crucial residues for dimerization and polymerase function of the enzyme, but have no impact when specifically deleted from the p66 subunit. These results demonstrate the b7–b8 loop of the p51 subunit in the formation of stable, functional heterodimeric enzyme which could be an attractive target for anti-HIV-1 drug development. J. Cell. Biochem. 109: 598–605, 2010.© 2009 Wiley-Liss, Inc.