5EU7
Crystal structure of HIV-1 integrase catalytic core in complex with Fab
Summary for 5EU7
| Entry DOI | 10.2210/pdb5eu7/pdb |
| Descriptor | Integrase, FAB Heavy Chain, FAB light chain, ... (4 entities in total) |
| Functional Keywords | integrase, fab, hiv, viral protein |
| Biological source | Human immunodeficiency virus 1 (HIV-1) More |
| Cellular location | Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585 |
| Total number of polymer chains | 6 |
| Total formula weight | 129823.00 |
| Authors | Galilee, M.,Griner, S.L.,Stroud, R.M.,Alian, A. (deposition date: 2015-11-18, release date: 2016-09-28, Last modification date: 2024-11-20) |
| Primary citation | Galilee, M.,Britan-Rosich, E.,Griner, S.L.,Uysal, S.,Baumgartel, V.,Lamb, D.C.,Kossiakoff, A.A.,Kotler, M.,Stroud, R.M.,Marx, A.,Alian, A. The Preserved HTH-Docking Cleft of HIV-1 Integrase Is Functionally Critical. Structure, 24:1936-1946, 2016 Cited by PubMed Abstract: HIV-1 integrase (IN) catalyzes viral DNA integration into the host genome and facilitates multifunctional steps including virus particle maturation. Competency of IN to form multimeric assemblies is functionally critical, presenting an approach for anti-HIV strategies. Multimerization of IN depends on interactions between the distinct subunit domains and among the flanking protomers. Here, we elucidate an overlooked docking cleft of IN core domain that anchors the N-terminal helix-turn-helix (HTH) motif in a highly preserved and functionally critical configuration. Crystallographic structure of IN core domain in complex with Fab specifically targeting this cleft reveals a steric overlap that would inhibit HTH-docking, C-terminal domain contacts, DNA binding, and subsequent multimerization. While Fab inhibits in vitro IN integration activity, in vivo it abolishes virus particle production by specifically associating with preprocessed IN within Gag-Pol and interfering with early cytosolic Gag/Gag-Pol assemblies. The HTH-docking cleft may offer a fresh hotspot for future anti-HIV intervention strategies. PubMed: 27692964DOI: 10.1016/j.str.2016.08.015 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.64 Å) |
Structure validation
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