The amyloid precursor-like protein 2 associates with the major histocompatibility complex class I molecule K(d).
Amyloid precursor-like protein 2 (APLP2) is a member of a protein family related to the amyloid precursor protein, which is implicated in Alzheimer's disease. Little is known about the physiological function of this protein family. The adenovirus E3/19K protein binds to major histocompatibility complex (MHC) class I antigens in the endoplasmic reticulum, thereby preventing their transport to the cell surface. In cells coexpressing E3/19K and the MHC K(d) molecule, K(d) is associated with E3/19K and two cellular protein species with masses of 100 and 110 kDa, termed p100/110. Interestingly, p100/110 are released from the complex upon the addition of K(d)-binding peptides, suggesting a role for these proteins in peptide transfer to MHC molecules. Here we demonstrate by microsequencing, reactivity with APLP2-specific antibodies, and comparison of biochemical parameters that p100/110 is identical to human APLP2. We further show that the APLP2/K(d) association does not require the physical presence of E3/19K. Thus, APLP2 exhibits an intrinsic affinity for the MHC K(d) molecule. Similar to the binding of MHC molecules to the transporter associated with antigen processing, complex formation between APLP2 and K(d) strictly depends upon the presence of beta(2)-microglobulin. Conditions that prolong the residency of K(d) in the endoplasmic reticulum lead to a profound increase of the association and a drastic reduction of APLP2 transport. Therefore, this unexpected interplay between these unrelated molecules may have implications for both MHC antigen and APLP2 function.
Sester
M
M
Max von Pettenkofer-Institut, Department of Virology, Genzentrum, Feodor-Lynen-Str. 25, 81377 München, Germany.
Feuerbach
D
D
Frank
R
R
Preckel
T
T
Gutermann
A
A
Burgert
H G
HG
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*
C489697:APLP1 protein, human; C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; C078201:Aplp1 protein, mouse; C492952:Aplp2 protein, mouse; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D009419:Nerve Tissue Proteins