PMID- 10677209
OWN - NLM
STAT- MEDLINE
DCOM- 20000313
LR  - 20190613
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 39
IP  - 7
DP  - 2000 Feb 22
TI  - The NMR structure of the nucleocapsid protein from the mouse mammary tumor virus 
      reveals unusual folding of the C-terminal zinc knuckle.
PG  - 1604-12
AB  - The nucleocapsid protein (NC) from the mouse mammary tumor virus (MMTV) has been 
      overexpressed in Escherichia coli and purified to homogeneity for structural 
      studies by nuclear magnetic resonance (NMR) spectroscopy. The protein contains 
      two copies of a conserved zinc-coordinating "CCHC array" or "zinc knuckle" motif 
      common to the nucleocapsid proteins of nearly all known retroviruses. The 
      residues comprising and adjacent to the zinc knuckles were assigned by standard 
      two-dimensional (1)H and three-dimensional (1)H-(15)N NMR methods; the rotational 
      dynamic properties of the protein were determined from (15)N relaxation 
      experiments, and distance restraints derived from the nuclear Overhauser effect 
      (NOE) data were used to calculate the three-dimensional structure. The (1)H-(1)H 
      NOE and (15)N relaxation data indicate that the two zinc knuckles do not interact 
      with each other, but instead behave as independently folded domains connected by 
      a flexible 13-residue linker segment. The proximal zinc knuckle folds in a manner 
      that is essentially identical to that observed previously for the two zinc 
      knuckles of the human immunodeficiency virus type 1 nucleocapsid protein and for 
      the moloney murine leukemia virus nucleocapsid zinc knuckle domain. However, the 
      distal zinc knuckle of MMTV NC exhibits a rare three-dimensional fold that 
      includes an additional C-terminal beta-hairpin. A similar C-terminal reverse 
      turn-like structure was observed recently in the distal zinc knuckle of the 
      Mason-Pfizer monkey virus nucleocapsid protein [Gao, Y., et al. (1998) Protein 
      Sci. 7, 2265-2280]. However, despite a high degree of sequence homology, the 
      conformation and orientation of the beta-hairpin in MMTV NC is significantly 
      different from that of the reverse turn in MPMV NC. The results support the 
      conclusion that structural features of NC zinc knuckle domains can vary 
      significantly among the different genera of retroviridae, and are discussed in 
      terms of the recent and surprising discovery that MMTV NC can facilitate 
      packaging of the HIV-1 genome in chimeric MMTV mutants.
FAU - Klein, D J
AU  - Klein DJ
AD  - Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, 
      University of Maryland Baltimore County, Baltimore, Maryland 21250, USA.
FAU - Johnson, P E
AU  - Johnson PE
FAU - Zollars, E S
AU  - Zollars ES
FAU - De Guzman, R N
AU  - De Guzman RN
FAU - Summers, M F
AU  - Summers MF
LA  - eng
SI  - PDB/1DSQ
SI  - PDB/1DSV
GR  - GM42561/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Nitrogen Isotopes)
RN  - 0 (Nucleocapsid Proteins)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Mammary Tumor Virus, Mouse/*chemistry
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nitrogen Isotopes
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Nucleocapsid Proteins/*chemistry
MH  - Peptide Fragments/*chemistry
MH  - Protein Conformation
MH  - *Protein Folding
MH  - Spectrum Analysis
MH  - Thermodynamics
MH  - *Zinc Fingers
EDAT- 2000/02/26 09:00
MHDA- 2000/03/18 09:00
CRDT- 2000/02/26 09:00
PHST- 2000/02/26 09:00 [pubmed]
PHST- 2000/03/18 09:00 [medline]
PHST- 2000/02/26 09:00 [entrez]
AID - bi9922493 [pii]
AID - 10.1021/bi9922493 [doi]
PST - ppublish
SO  - Biochemistry. 2000 Feb 22;39(7):1604-12. doi: 10.1021/bi9922493.