© 2006 The Japanese Biochemical Society.
Regular Paper |
Structural Analysis of a Mutant of the HIV-1 Integrase Zinc Finger Domain That Forms a Single Conformation
1 Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016; and 2 Department of Immunotherapeutics, Medical Research Division, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519
* To whom correspondence should be addressed. Phone/Fax: +81-47-478-0425, E-mail: gkawai{at}sea.it-chiba.ac.jp
HIV-1 integrase consists of three functional domains, an N-terminal zinc finger domain, a catalytic core domain and a C-terminal DNA binding domain. NMR analysis of an isolated N-terminal domain (IN1–55) has shown that IN1–55 exists in two conformational states [E and D forms; Cai et al. (1997) Nat. Struct. Biol. 4, 567–577]. The two forms differ in the coordination of the zinc ion by two histidine residues. In the present study, structural analysis of a mutant of IN1–55, Y15A, by NMR spectroscopy indicated that the mutant protein folds correctly but takes only the E form. Since the Y15A mutation abrogates the HIV-1 infectivity, Y15 might have some important role in the full-length integrase activity during the virus infection cycle. Our results suggest a possible role of Y15 in structural transition between the E and D forms of HIV-1 integrase to allow the optimal tetramerization.