3O4N

Crystal structure of the Rous Associated Virus Integrase catalytic domain in MES buffer pH 6.0

3O4N の概要

• エントリーDOI: 10.2210/pdb3o4n/pdb
• 分子名称: integrase, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ZINC ION, ... (4 entities in total)
• 機能のキーワード: dna integration process, dna binding protein
• 由来する生物種: Rous sarcoma virus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33046.95

構造登録者

Ballandras, A.,Robert, X.,Gouet, P. (登録日: 2010-07-27, 公開日: 2011-08-31, 最終更新日: 2023-09-06)

主引用文献

Ballandras, A.,Moreau, K.,Robert, X.,Confort, M.P.,Merceron, R.,Haser, R.,Ronfort, C.,Gouet, P.
A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly.
Plos One, 6:e23032-e23032, 2011

PubMed Abstract: Integrase (IN) is an important therapeutic target in the search for anti-Human Immunodeficiency Virus (HIV) inhibitors. This enzyme is composed of three domains and is hard to crystallize in its full form. First structural results on IN were obtained on the catalytic core domain (CCD) of the avian Rous and Sarcoma Virus strain Schmidt-Ruppin A (RSV-A) and on the CCD of HIV-1 IN. A ribonuclease-H like motif was revealed as well as a dimeric interface stabilized by two pairs of α-helices (α1/α5, α5/α1). These structural features have been validated in other structures of IN CCDs. We have determined the crystal structure of the Rous-associated virus type-1 (RAV-1) IN CCD to 1.8 Å resolution. RAV-1 IN shows a standard activity for integration and its CCD differs in sequence from that of RSV-A by a single accessible residue in position 182 (substitution A182T). Surprisingly, the CCD of RAV-1 IN associates itself with an unexpected dimeric interface characterized by three pairs of α-helices (α3/α5, α1/α1, α5/α3). A182 is not involved in this novel interface, which results from a rigid body rearrangement of the protein at its α1, α3, α5 surface. A new basic groove that is suitable for single-stranded nucleic acid binding is observed at the surface of the dimer. We have subsequently determined the structure of the mutant A182T of RAV-1 IN CCD and obtained a RSV-A IN CCD-like structure with two pairs of buried α-helices at the interface. Our results suggest that the CCD of avian INs can dimerize in more than one state. Such flexibility can further explain the multifunctionality of retroviral INs, which beside integration of dsDNA are implicated in different steps of the retroviral cycle in presence of viral ssRNA.

PubMed: 21857987
DOI: 10.1371/journal.pone.0023032

実験手法

X-RAY DIFFRACTION (1.8 Å)