title: X-ray crystal structure of the N-terminal region of Moloney murine leukemia virus integrase and its implications for viral DNA recognition.
abstract: The retroviral integrase (IN) carries out the integration of a dsDNA copy of the viral genome into the host DNA, an essential step for viral replication. All IN proteins have three general domains, the N-terminal domain (NTD), the catalytic core domain, and the C-terminal domain. The NTD includes an HHCC zinc finger-like motif, which is conserved in all retroviral IN proteins. Two crystal structures of Moloney murine leukemia virus (M-MuLV) IN N-terminal region (NTR) constructs that both include an N-terminal extension domain (NED, residues 1-44) and an HHCC zinc-finger NTD (residues 45-105), in two crystal forms are reported. The structures of IN NTR constructs encoding residues 1-105 (NTR1-105) and 8-105 (NTR8-105) were determined at 2.7 and 2.15 Å resolution, respectively and belong to different space groups. While both crystal forms have similar protomer structures, NTR1-105packs as a dimer and NTR8-105packs as a tetramer in the asymmetric unit. The structure of the NED consists of three anti-parallel β-strands and an α-helix, similar to the NED of prototype foamy virus (PFV) IN. These three β-strands form an extended β-sheet with another β-strand in the HHCC Zn2+binding domain, which is a unique structural feature for the M-MuLV IN. The HHCC Zn2+binding domain structure is similar to that in HIV and PFV INs, with variations within the loop regions. Differences between the PFV and MLV IN NEDs localize at regions identified to interact with the PFV LTR and are compared with established biochemical and virological data for M-MuLV. Proteins 2017; 85:647-656. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.|Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.|Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.
authors.forename: Rongjin
authors.initials: R
authors.lastname: Guan
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.
authors.forename: Sriram
authors.initials: S
authors.lastname: Aiyer
authors.affiliation: Department of Biochemistry, Robert Wood Johnson Medical School, UMDNJ, Piscataway, New Jersey, 08854.
authors.forename: Marie L
authors.initials: ML
authors.lastname: Cote
authors.affiliation: Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.|Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.|Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.|Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.|Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.
authors.forename: Mei
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.|Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.|Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Acton
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Roth
authors.affiliation: Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.|Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.|Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854.|Department of Biochemistry, Robert Wood Johnson Medical School, UMDNJ, Piscataway, New Jersey, 08854.
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004279:DNA, Viral / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D019426:Integrases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008979:Moloney murine leukemia virus / Q000737:chemistry* / Q000201:enzymology; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D004279:DNA, Viral; D011994:Recombinant Proteins; D014764:Viral Proteins; D019426:Integrases
keywords: DNA integration; N-terminal domain; N-terminal extension domain; Zn2+ finger protein; homology modeling; retroviral integrase