Structure and function of the C-terminal PABC domain of human poly(A)-binding protein

We have determined the solution structure of the C-terminal quarter of huma n poly(A)-binding protein (hPABP). The protein fragment contains a protein domain, PABC [for poly(A)-binding protein C-terminal domain], which is also found associated with the HECT family of ubiquitin ligases. By using pepti des derived from PABP interacting protein (Paip) 1, Paip2, and eRF3, we sho w that PABC functions as a peptide binding domain. We use chemical shift pe rturbation analysis to identify the peptide binding site in PABC and the ma jor elements involved in peptide recognition. From comparative sequence ana lysis of PABC-binding peptides, we formulate a preliminary PABC consensus s equence and identify human ataxin-2, the protein responsible for type 2 spi nocerebellar ataxia (SCA2), as a potential PABC ligand.