( tein from folding up; then they are sla...)New technique boosts size of proteins that can be analyzed

The top-down approach rivals the commonly used "bottom-up" approach, in which proteins are first broken down, or digested, enzymatically into smaller units of five to 20 amino acids. These pieces are then introduced into the mass spectrometer where researchers can match masses of those pieces to known sequences and identify the proteins.

However, this approach reveals less information concerning modifications to proteins. Such important cellular processes as oxidation and acetylation of proteins add chemical groups and alter how a protein functions, such as modifying an enzymatic pathway. The bottom-up approach is limited because the samples seldom have masses that represent all the pieces of the protein, and masses can usually be matched to several combinations of pieces and modifications. Therefore, the method rarely locates all modifications in newly isolated proteins.

"Each approach has different strengths and weaknesses," said Mi Jin, a postdoctoral associate in chemistry and chemical biology and one of the paper's lead authors with fellow graduate student Xuemei Han. Jin said that the bottom-up approach is often used for larger scale studies of proteins because it can identify a large number of proteins from a sample, but it does not provide a complete picture of each protein. The top-down approach, on the other hand, measures the whole protein and thus provides more confident identifications; it is also better at revealing modifications and mutations, where there might be a mistake or addition in the sequence. The new approach can also provide sequence information on a protein from scratch when it is not present in any database.