       Document 0739
 DOCN  M9620739
 TI    HIV nuclear import is governed by the phosphotyrosine-mediated binding
       of matrix to the core domain of integrase.
 DT    9602
 AU    Gallay P; Swingler S; Song J; Bushman F; Trono D; Infectious Disease
       Laboratory, Salk Institute for Biological; Studies, La Jolla, California
       92037, USA.
 SO    Cell. 1995 Nov 17;83(4):569-76. Unique Identifier : AIDSLINE
       MED/96069858
 AB    The karyophilic properties of the viral matrix (MA) protein govern HIV
       nuclear import in nondividing cells such as macrophages. A critical
       regulator of this process is the C-terminal tyrosine phosphorylation of
       MA during virus maturation. Here, we reveal the mechanism of this
       phenomenon, by demonstrating that tyrosine phosphorylation induces the
       binding of MA to integrase (IN). This leads to the incorporation of MA
       molecules into virus cores, and subsequently into uncoated viral
       nucleoprotein complexes. A direct interaction between
       tyrosine-phosphorylated MA and the central domain of IN can be
       demonstrated in vitro. It is blocked by phosphotyrosine, indicating that
       IN recognizes the phosphorylated C-terminal residue of MA. These results
       explain how the karyophilic potential of MA is conferred to the HIV
       nucleoprotein complex.
 DE    Base Sequence  Biological Transport/PHYSIOLOGY  Cell
       Nucleus/METABOLISM/*VIROLOGY  DNA Nucleotidyltransferases/*METABOLISM
       Hela Cells/PHYSIOLOGY  Human  HIV-1/*METABOLISM  Molecular Sequence Data
       Nucleoproteins/METABOLISM  Phosphorylation  Phosphotyrosine/*METABOLISM
       Protein Binding/PHYSIOLOGY  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  T-Lymphocytes/PHYSIOLOGY  Viral Matrix
       Proteins/METABOLISM  Virus Integration/*PHYSIOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

