PMID- 18073204
OWN - NLM
STAT- MEDLINE
DCOM- 20080331
LR  - 20211020
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 6
DP  - 2008 Feb 8
TI  - The tyrosine binding pocket in the adaptor protein 1 (AP-1) mu1 subunit is 
      necessary for Nef to recruit AP-1 to the major histocompatibility complex class I 
      cytoplasmic tail.
PG  - 3011-3022
LID - S0021-9258(20)69763-0 [pii]
LID - 10.1074/jbc.M707760200 [doi]
AB  - To evade the anti-human immunodeficiency virus (HIV) immune response, the HIV Nef 
      protein disrupts major histocompatibility complex class I (MHC-I) trafficking by 
      recruiting the clathrin adaptor protein 1 (AP-1) to the MHC-I cytoplasmic tail. 
      Under normal conditions AP-1 binds dileucine and tyrosine signals (YXX phi 
      motifs) via physically separate binding sites. In the case of the Nef-MHC-I 
      complex, a tyrosine in the human leukocyte antigen (HLA)-A2 cytoplasmic tail 
      ((320)YSQA) and a methionine in Nef (Met(20)) are absolutely required for AP-1 
      binding. Also present in Nef is a dileucine motif, which does not normally affect 
      MHC-I trafficking and is not needed to recruit AP-1 to the Nef-MHC-I-complex. 
      However, evidence is presented here that this dileucine motif can be activated by 
      fusing Nef to the HLA-A2 tail in cis. Thus, the inability of this motif to 
      function in trans likely results from a structural change that occurs when Nef 
      binds to the MHC-I cytoplasmic tail. The physiologically relevant 
      tyrosine-dependent recruitment of AP-1 to MHC-I, which occurs whether Nef is 
      present in cis or trans, was stabilized by the acidic and polyproline domains 
      within Nef. Additionally, amino acids Ala(324) and Asp(327) in the cytoplasmic 
      tails of HLA-A and (but not HLA-C and HLA-E) molecules also stabilized AP-1 
      binding. Finally, mutation of the tyrosine binding pocket in the mu subunit of 
      AP-1 created a dominant negative inhibitor of Nef-induced down-modulation of 
      HLA-A2 that disrupted binding of wild type AP-1 to the Nef-MHC-I complex. Thus, 
      these data provide evidence that Nef binding to the MHC-I cytoplasmic tail 
      stabilizes the interaction of a tyrosine in the MHC-I cytoplasmic tail with the 
      natural tyrosine binding pocket in AP-1.
FAU - Wonderlich, Elizabeth R
AU  - Wonderlich ER
AD  - Cellular and Molecular Biology Graduate Program, University of Michigan, Ann 
      Arbor, Michigan 48109.
FAU - Williams, Maya
AU  - Williams M
AD  - Cellular and Molecular Biology Graduate Program, University of Michigan, Ann 
      Arbor, Michigan 48109.
FAU - Collins, Kathleen L
AU  - Collins KL
AD  - Cellular and Molecular Biology Graduate Program, University of Michigan, Ann 
      Arbor, Michigan 48109; Department of Microbiology and Immunology, University of 
      Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine, University 
      of Michigan, Ann Arbor, Michigan 48109. Electronic address: klcollin@umich.edu.
LA  - eng
GR  - T32 GM007315/GM/NIGMS NIH HHS/United States
GR  - R01AI46998/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071211
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Protein Complex 1)
RN  - 0 (Gene Products, nef)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 42HK56048U (Tyrosine)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Adaptor Protein Complex 1/*chemistry
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Cytoplasm/metabolism
MH  - Gene Expression Regulation
MH  - Gene Products, nef/*chemistry
MH  - Histocompatibility Antigens Class I/*chemistry
MH  - Humans
MH  - Leucine/chemistry
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Sequence Homology, Amino Acid
MH  - Tyrosine/*chemistry
EDAT- 2007/12/13 09:00
MHDA- 2008/04/01 09:00
CRDT- 2007/12/13 09:00
PHST- 2007/12/13 09:00 [pubmed]
PHST- 2008/04/01 09:00 [medline]
PHST- 2007/12/13 09:00 [entrez]
AID - S0021-9258(20)69763-0 [pii]
AID - 10.1074/jbc.M707760200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Feb 8;283(6):3011-3022. doi: 10.1074/jbc.M707760200. Epub 2007 
      Dec 11.