AMINO-ACID-SEQUENCE ANALYSIS OF AMYLOID PROTEIN-A (AA) FROM CATS (CAPTIVE CHEETAHS - ACINONYX-JUBATUS) WITH A HIGH PREVALENCE OF AA AMYLOIDOSIS

Systemic AA amyloidosis is relatively uncommon in domestic cars, but a relatively high prevalence of this form of amyloidosis has been docum ented in Abyssinian cats and, most recently, in captive cheetahs. Thes e cats thus provide an opportunity to identify and compare amino acid sequence differences in the respective AA proteins that may potentiall y affect the amyloidogenic process. In this study we determined the co mplete amino acid sequence of cheetah protein AA (positions 1-90). The se positions conform to positions 2-83 of human proteins apoSAA/AA in that the respective cat proteins are N-terminally one residue shorter than the human protein and have an eight amino acid insert between res idues conforming to positions 69 and 70 of human apoSAA/AA. Comparison of the protein AA sequence of the cheetah with confirmed protein AA s equences from Abyssinian and/or domestic short-haired (DSH) cats revea led amino acid variations at positions 2, 30, 43, 49, 54, 69e, 69g and 81 (using human numbering). AA proteins of the cheetah and Abyssinian cat (both with high prevalences of AA amyloidosis) had concordance at five of these eight positions of variability (i.e., positions 30, 43, 49, 54, and 69e). Concordance between the cheetah and DSH cat was res tricted to the proline and alanine residues associated with positions of residue heterogeniety (positions 49 and 54, respectively) in DSH ca t protein AA. The glutamic acid residue unique to DSH cat protein AA a t position 43 is special interest in that it occurs within a strictly conserved region of protein AA homology in the cheetah, Abyssinian cat , and all other species compared. These sequence differences of the DS H cat may provide further evidence of possible link between certain ap oSAA structural motifs and AA amyloidogenesis.