Our twin research groups (Collins, York; Ritz-Timme Düsseldorf) focus on the recovery of proteins from aged remains; often very aged remains - from forensic and archaeological samples. Our peculiar focus on the persistence and decay of proteins in these old samples has given us particular insights into the key degradation reactions which occur to proteins post-synthesis.
As soon as polypeptide chains are formed they will begin to undergo chemical changes deleterious to their function; these include chemical hydrolysis, condensation, side chain modification and racemization. In most cases these reactions are so slow that they occur at near undetectable levels and do not interfere with function, whilst repair enzymes can correct some, but not all modifications. Extracellular proteins because tend to be longer lived and lack access to the same suite of repair enzymes will be expected to accumulate damage to levels that can be readily detected.
Using a range of analytical techniques, we have been trying to obtain a broad overview of key processes. Of the alternative mechanisms, we have focused much of our effort on racemization, notably of aspartic acid. Racemization is both easy to monitor and can occur very rapidly. It accompanies deamidation of asparaginyl residues and can lead not only to the formation of D-aspartyl but also D-and L-isoaspartyl residues. These changes in primary structure can impact upon higher level organization of the protein.
We have examined levels of D-Asx in a variety of extracellular tissues, principally form mineralized hard tissues which are recovered from forensic and archaeological sites (dentine and bone). These tissues display strong age dependent accumulations of D-Asx both post-mortem and in life. More recently we have observed similar age dependent in vivo accumulation of D-Asx in soft tissues, suggesting that this is an inevitable consequence of ageing which is either tolerated or irreparable.
Does this increasing deterioration of extra-cellular proteins matter and if so what strategies could be used to minimise the rate of accumulation?