Protein modiﬁcation in proteomics
Almost all proteins are modiﬁed in some way during or after synthesis, either by cleavage of the polypeptide backbone or chemical modiﬁcation of speciﬁc amino acid side chains. This phenomenon, which is known as post-translational modiﬁcation (PTM), provides a direct mechanism for the regulation of protein activity and greatly enhances the structural diversity and functionality of proteins by providing a larger repertoire of chemical properties than is possible using the 20 standard amino acids speciﬁed by the genetic code. Several hundred different forms of chemical modiﬁcation have been documented, some of which inﬂuence protein structure, some of which are required for proteins to interact with ligands or each other, some of which have a direct impact on biochemical activity and some that help sort proteins into different subcellular compartments (Table 8.1). Modiﬁcations are often permanent, but some, such as phosphorylation, are reversible and can be used to switch protein activity on and off in response to intracellular and extracellular signals. Post-translational modiﬁcation is therefore a dynamic phenomenon with a central role in many biological processes. Importantly, inappropriate post-translational modiﬁcation is often associated with disease, and particular post-translational variants can be used as disease biomarkers or therapeutic targets (Chapter 10). While the above types of modiﬁcation are typical of normal physiological processes, others are associated with damage, aging or occur as artifacts when proteins are extracted in particular buffers.