Crystal structure of the conserved core of HIV-1 Nef complexed with a Src family SH3 domain.
The crystal structure of the conserved core of HIV-1 Nef has been determined in complex with the SH3 domain of a mutant Fyn tyrosine kinase (a single amino acid substitution, Arg-96 to isoleucine), to which Nef binds tightly. The conserved PxxP sequence motif of Nef, known to be important for optimal viral replication, is part of a polyproline type II helix that engages the SH3 domain in a manner resembling closely the interaction of isolated peptides with SH3 domains. The Nef-SH3 structure also reveals how high affinity and specificity in the SH3 interaction is achieved by the presentation of the PxxP motif within the context of the folded structure of Nef.
Lee
C H
CH
The Rockefeller University, New York, New York 10021, USA.
Saksela
K
K
Mirza
U A
UA
Chait
B T
BT
Kuriyan
J
J
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D015693:Gene Products, nef / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D054311:nef Gene Products, Human Immunodeficiency Virus; D018909:src Homology Domains
D015693:Gene Products, nef; D011518:Proto-Oncogene Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D007532:Isoleucine; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn