1EX4

HIV-1 INTEGRASE CATALYTIC CORE AND C-TERMINAL DOMAIN

Summary for 1EX4

• Entry DOI: 10.2210/pdb1ex4/pdb
• Descriptor: INTEGRASE, 3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE (3 entities in total)
• Functional Keywords: sh3-like domain, nonspecific dna binding beta sheet, cis-proline, viral protein
• Biological source: Human immunodeficiency virus 1
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P04585
• Total number of polymer chains: 2
• Total formula weight: 55313.53

Authors

Chen, J.C.-H.,Krucinski, J.,Miercke, L.J.W.,Finer-Moore, J.S.,Tang, A.H.,Leavitt, A.D.,Stroud, R.M. (deposition date: 2000-04-28, release date: 2000-06-07, Last modification date: 2024-02-07)

Primary citation

Chen, J.C.,Krucinski, J.,Miercke, L.J.,Finer-Moore, J.S.,Tang, A.H.,Leavitt, A.D.,Stroud, R.M.
Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA binding.
Proc.Natl.Acad.Sci.USA, 97:8233-8238, 2000

PubMed Abstract: Insolubility of full-length HIV-1 integrase (IN) limited previous structure analyses to individual domains. By introducing five point mutations, we engineered a more soluble IN that allowed us to generate multidomain HIV-1 IN crystals. The first multidomain HIV-1 IN structure is reported. It incorporates the catalytic core and C-terminal domains (residues 52-288). The structure resolved to 2.8 A is a Y-shaped dimer. Within the dimer, the catalytic core domains form the only dimer interface, and the C-terminal domains are located 55 A apart. A 26-aa alpha-helix, alpha6, links the C-terminal domain to the catalytic core. A kink in one of the two alpha6 helices occurs near a known proteolytic site, suggesting that it may act as a flexible elbow to reorient the domains during the integration process. Two proteins that bind DNA in a sequence-independent manner are structurally homologous to the HIV-1 IN C-terminal domain, suggesting a similar protein-DNA interaction in which the IN C-terminal domain may serve to bind, bend, and orient viral DNA during integration. A strip of positively charged amino acids contributed by both monomers emerges from each active site of the dimer, suggesting a minimally dimeric platform for binding each viral DNA end. The crystal structure of the isolated catalytic core domain (residues 52-210), independently determined at 1.6-A resolution, is identical to the core domain within the two-domain 52-288 structure.

PubMed: 10890912
DOI: 10.1073/pnas.150220297

Experimental method

X-RAY DIFFRACTION (2.8 Å)