PMID- 10497202
OWN - NLM
STAT- MEDLINE
DCOM- 19991102
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 40
DP  - 1999 Oct 1
TI  - CCR5 HIV-1 coreceptor activity. Role of cooperativity between residues in
      N-terminal extracellular and intracellular domains.
PG  - 28413-9
AB  - Human (H-) CCR5 is the primary coreceptor for ENV-mediated fusion by R5 strains
      of human immunodeficiency virus type 1, whereas mouse (M-) CCR5 lacks this
      function. An array of 23 H/M-CCR5 hybrids containing increasing amounts of H-CCR5
      extending from the N terminus generated by random chimeragenesis had a biphasic
      pattern of coreceptor activity with JRFL and 89.6, revealing active regions in
      the N-terminal extracellular domain (N-ED) and at the junction of cytoplasmic
      loop 3. The M-CCR5 mutant in which divergent residues were replaced with the
      corresponding H-CCR5 N-ED sequence (NyYTsE) gained coreceptor function in fusion 
      but not infection experiments. A M-CCR5 double mutant with substitution of human 
      sequences for divergent residues from the N-ED and cytoplasmic loop 3 had
      augmented coreceptor activity in fusion assays and gain of function in infection 
      experiments. The SIV-251 ENV utilized H- and M-CCR5 and variants. Flow cytometric
      analysis of M-CCR5 mutants and bifunctional receptors composed of CD4 domains
      fused to M-CCR5 mutants excluded the possibility that differences in coreceptor
      activity resulted from variations in cell surface expression. These results
      demonstrate that the coreceptor activity of the H-CCR5 N-ED is modulated by
      intracellular residues, illustrating the complexity of CCR5 requirements for
      interaction with ENV.
FAU - Wang, Z
AU  - Wang Z
AD  - Henry Vogt Cancer Research Institute, University of Louisville, Louisville,
      Kentucky 40202, USA.
FAU - Lee, B
AU  - Lee B
FAU - Murray, J L
AU  - Murray JL
FAU - Bonneau, F
AU  - Bonneau F
FAU - Sun, Y
AU  - Sun Y
FAU - Schweickart, V
AU  - Schweickart V
FAU - Zhang, T
AU  - Zhang T
FAU - Peiper, S C
AU  - Peiper SC
LA  - eng
GR  - AI 41346/AI/NIAID NIH HHS/United States
GR  - KO8 HL03923/HL/NHLBI NIH HHS/United States
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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Receptors, CCR5)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
SB  - X
MH  - Amino Acid Sequence
MH  - Animals
MH  - HIV-1/*metabolism
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Receptors, CCR5/chemistry/genetics/*metabolism
MH  - Recombinant Fusion Proteins/chemistry/metabolism
EDAT- 1999/09/25 00:00
MHDA- 1999/09/25 00:01
CRDT- 1999/09/25 00:00
PHST- 1999/09/25 00:00 [pubmed]
PHST- 1999/09/25 00:01 [medline]
PHST- 1999/09/25 00:00 [entrez]
AID - 10.1074/jbc.274.40.28413 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 1;274(40):28413-9. doi: 10.1074/jbc.274.40.28413.