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The modification of amino acids
- Secreted proteins, lumen proteins and membrane proteins are frequently chemically modified both co-translationally and post-translationally. These modifications can significantly change the properties of a protein (charge, hydrophobicity, conformation and / or stability).
Some of these isoforms of a protein can be detected by gel electrophoresis (phosphorylation, for example, increases the negative charge of the protein), but glycosylation does not change the charge of the protein. Glycosylation can be detected by adding antibodies that recognize certain epitopes of a protein (e.g. sugar residues) to the protein. Lectins and digoxigenin also bind to sugar residues. Sometimes, however, only the mass spectrometric analysis provides information about the type and exact position of the modification in the molecule.
The meaning of the modifications: some examples
- The activity of many regulatory proteins is controlled by the phosphorylation of certain amino acids. In eukaryotes it is primarily the phosphorylation of Ser, Thr, Tyr or His residues of proteins that are involved in signaling cascades. In the case of bacteria, it is mainly Asp and His residues (in two-component regulator systems).
- Adenylation (addition of AMP) or uridylation (addition of UMP) can also influence the activity of a protein, for example in the case of glutamine synthetase and the regulatory protein PII in the nitrogen metabolism of E. coli.
- Modifications also play an important role for structural proteins. The hydroxylation of collagen to hydroxy collagen is essential for ligament and tissue stability. If the corresponding enzyme, prolyl-4-hydroxylase, is missing in the organism, serious defects occur (e.g. scurvy).
- Tab. 1
|Cell structure||Compartment||Example of modification|
|Nucleus||Intracellular||Acetylation (e.g. of histones on the ε-amino group)|
|Lysosome||Intracellular||N-linkage with mannose-6-phosphate|
|Chloroplast||Intracellular||N-formyl acylation, N- and O-linkage with oligosaccharides, attachment of sulfate groups, palmitoylation|
|Endoplasmic reticulum||Intracellular||N-linkage with oligosaccharides, attachment of GPI anchors|
|Cytosol||Intracellular||Acetylation, methylation, phosphorylation|
|Plasma membrane||Cell surface||N- and O-glycosylation, attachment of GPI anchors|
|extracellular fluid||Extracellular||N- and O-glycosylation, acetylation, phosphorylation|
|extracellular matrix||Extracellular||N- and O-glycosylation, hydroxylation, phosphorylation|