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24
A Fifth Adaptor Protein Complex
Jennifer Hirst 1 , Joel Dacks 2 , Margaret Robinson 1 .
University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 0XY,
United Kingdom 1 , Department of Cell Biology, University of Alberta, Edmonton T6G 2H7,
Canada 2
Abstract:
In addition to adaptor protein (AP) complexes there are several other families of proteins that
contain µ homology domains (MHDs), including the monomeric stonins, and a family that
includes the mammalian proteins FCHO1, FCHO2, and SGIP1. The least characterised of the
MHD proteins is encoded in humans by a gene on chromosome 14 (C14orf108). Because so far
all MHD proteins have been shown to be involved in membrane traffic, it seemed likely that the
same would be true for C14orf108. We have been able to show that that C14orf108 has more in
common with the µ-adaptins than with other MHD-containing proteins. C14orf108’s homology
to the µ-adaptins extends upstream beyond the MHD, and secondary structure predictions
indicate that the µ-adaptins and C14orf108 adopt very similar folds. In addition, C14orf108
binds to a previously uncharacterised protein which is homologous to the β-adaptins and has an
almost identical predicted secondary structure. Further evidence for the interaction between
C14orf108 and the β-like adaptin comes from the similar distribution of the two genes in
eukaryotes from five different supergroups, and from their similar knockdown phenotypes. Our
results suggest the possibility of a fifth adaptor complex, and we are trying to determine if ‘AP-5’
like the other AP complexes exists as a heterotetramer of 4 subunits, and whether it associates
with clathrin.