       Document 0306
 DOCN  M94A0306
 TI    Structures of an HIV and MHC binding fragment from human CD4 as refined
       in two crystal lattices.
 DT    9412
 AU    Ryu SE; Truneh A; Sweet RW; Hendrickson WA; Department of Biochemistry
       and Molecular Biophysics, Columbia; University, New York, NY 10032.
 SO    Structure. 1994 Jan 15;2(1):59-74. Unique Identifier : AIDSLINE
       MED/94356446
 AB    BACKGROUND: The T-cell surface glycoprotein CD4 interacts with class II
       molecules of the major histocompatibility complex (MHC) enhancing the
       signal for T-cell activation. Human CD4 also interacts, at high
       affinity, with the HIV envelope glycoprotein, gp120, to mediate T-cell
       infection by HIV. Crystal structures of amino-terminal two-domain (D1D2)
       fragments of human CD4, which contain the residues implicated in HIV and
       MHC interactions, have been reported earlier. RESULTS: We have
       determined the crystal structure of a new D1D2 construct by molecular
       replacement from a previously described crystal structure of D1D2. This
       structure has more uniform lattice contacts than are in the first. This
       gives an improved image of domain D2, which in turn has permitted
       further refinement of the initial structure at 2.3 A resolution against
       a more complete data set. The structure of the second crystal form was
       also refined at 2.9 A resolution. In both models, all residues from 1 to
       178 are now well defined, including the loop regions in D2. CONCLUSIONS:
       Similarities of the molecular structure in the two lattices suggest that
       the D1D2 fragment works as a unit, with segmental flexibility largely
       restricted to the junction between domains D2 and D3. Variability of
       conformation in loops, including those implicated in MHC and HIV
       binding, requires an 'induced fit' in these interactions. Well defined
       density for the exposed side chain of Phe43 in both crystals confirms a
       prominent role for this residue in gp120 binding.
 DE    Amino Acid Sequence  Antigens, CD/*CHEMISTRY/METABOLISM  Antigens,
       CD4/*CHEMISTRY/METABOLISM  Binding Sites  Calorimetry  Computer Graphics
       Crystallography, X-Ray/METHODS  Human  Hydrogen Bonding  HIV/*METABOLISM
       *Major Histocompatibility Complex  Models, Molecular  Molecular Sequence
       Data  Peptide Fragments/*CHEMISTRY/METABOLISM  *Protein Conformation
       Software  Support, U.S. Gov't, Non-P.H.S.  JOURNAL ARTICLE

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

