TPC_edits.biochemistry-basics.md

content/03.biochemistry-basics.md

@@ -7,27 +7,28 @@ They perform various functions in living organisms ranging from structural roles
 Proteins are made up of 20 different amino acids (not counting pyrrolysine and selenocysteine, which only occur in specific organisms) and their sequence is encoded in their corresponding genes.
 The human genome encodes approximately 19,778 of the predicted canonical proteins coded in the human genome [@PMID:36318223].
 Each protein is present at a different abundance depending on the cell type.
-Previous studies have shown that the concentration range of proteins can span over a range of at least seven orders of magnitude to up to 20 000 000 copies per cell, and that their distribution is tissue-specific [@DOI:10.1038/msb.2011.82;@DOI:10.1016/j.cell.2020.08.036].
-Proteins can span more than 10 orders of magnitude in human blood, while a few protein make up most of the protein by weight in these fluids, making blood and plasma proteomics one of the most difficult matrices. 
-Due to genetic variations, alternative splicing and post-translational modifications (PTMs), multiple different proteoforms can be produced from a single gene (**Figure 1**) [@DOI:10.1038/nmeth.2369; @DOI:10.1038/s41587-023-01714-x]. 
+Previous studies have shown that the concentration range of proteins can span over a range of at least seven orders of magnitude to up to 20,000,000 copies per cell, and that their distribution is tissue-specific [@DOI:10.1038/msb.2011.82;@DOI:10.1016/j.cell.2020.08.036].
+Protein abundances can span more than 10 orders of magnitude in human blood, while a few protein make up most of the protein by weight in these fluids, making blood and plasma proteomics one of the most difficult matrices. 
+Due to genetic variation, alternative splicing during gene transcription, and co- and post-translational modifications (PTMs), multiple different proteoforms can be produced from a single gene (**Figure 1**) [@DOI:10.1038/nmeth.2369; @DOI:10.1038/s41587-023-01714-x]. 
 
 ![**Proteome Complexity.**
-There is more than one protein product from each gene product due to alternative splicing and post-translational modifications. 
-This means there are likely many more unique "proteoforms" than there are genes. 
-Some estimates are upwards of 1,000,000 unique possible protein sequences.](images/intro-centralDogma-proteoforms.png){#fig:proteoforms tag="1" width="100%"}
+Each gene may be expressed in the form of multiple protein products, or proteoforms, through alternative splicing and incorporation of post-translational modifications.
+As such, there are many more unique proteoforms than there are genes.
+While there exist 20,000 - 23,000 coding genes in the human genome, upwards of 1,000,000 unique human proteoforms may exist.
+The study of the structure, function, and spatial and temporal regulation of these proteins is the subject of mass spectrometry-based proteomics](images/intro-centralDogma-proteoforms.png){#fig:proteoforms tag="1" width="100%"}
 
 #### PTMs
 
-After protein biosynthesis, enzymatic and nonenzymatic processes change the protein sequence through proteolysis or covalent chemical modification of the amino acid side chains. 
-PTMs are important biological regulators contributing to the diversity and function of the cellular proteome. 
+After protein biosynthesis, enzymatic and nonenzymatic processes change the protein sequence through proteolysis or covalent chemical modification of amino acid side chains. 
+Post-translational modifications (PTMs) are important biological regulators contributing to the diversity and function of the cellular proteome. 
 Proteins can be post-translationally modified through enzymatic and non-enzymatic reactions _in vivo_ and _in vitro_ [@doi:10.1093/database/baab012]. 
-PTMs can be reversible or irreversible, and they change protein function in several ways, for example, by altering substrate–enzyme(s) interactions, subcellular localization or protein-protein interactions [@PMID:33826699; @PMID:24217768]. 
+PTMs can be reversible or irreversible, and they change protein function in several ways, for example by altering substrate–enzyme interactions, subcellular localization or protein-protein interactions [@PMID:33826699; @PMID:24217768]. 
 
-More than biological 400 PTMs have been discovered in both prokaryotic and eukaryotic cells. 
+More than 400 PTMs have been discovered in both prokaryotic and eukaryotic cells. 
 These modifications are crucial in controlling protein functions and signal transduction pathways [@PMID:23887885]. 
-The most commonly studied and biologically relevant post-translational modifications include ubiquitination (Lys, Cys, Ser, Thr, N-term), succinylation (Lys), methylation (Arg, Lys, His, Glu, Asn, Cys), disulfide bonds (Cys-Cys), oxidation (any amino acid, but especially Met, Trp, His, Cys), phosphorylation (Ser, Thr, Tyr, His), acetylation (Lys, N-term), glycosylation (Arg, Asp, Cys, Ser, Thr, Tyr, Trp) and lipidation.
+The most commonly studied and biologically relevant post-translational modifications include ubiquitination (Lys, Cys, Ser, Thr, N-term), succinylation (Lys), methylation (Arg, Lys, His, Glu, Asn, Cys), disulfide bonds (Cys-Cys), oxidation (any amino acid, but especially Met, Trp, His, Cys), phosphorylation (Ser, Thr, Tyr, His), acetylation (Lys, N-term), glycosylation (Arg, Asp, Cys, Ser, Thr, Tyr, Trp) and lipidation [@DOI:https://doi.org/10.1042/BCJ20220251].
 
-Post-translational modification of a protein can alter its function, activity, structure, location and interactions. 
+Post-translational modification of a protein can alter its function, activity, structure, spatiotemporal status and interaction with proteins or small molecules. 
 PTMs alter signal transduction pathways and gene expression control [@PMID:28656226] regulation of apoptosis [@PMID:23088365; @PMID:11368354] by phosphorylation. 
 Ubiquitination regulates protein degradation [@PMID:16738015], SUMOylation regulates chromatin structure, DNA repair, transcription, cell-cycle progression [@PMID:26601932; @PMID:29079793], and palmitoylation regulates maintenance of the structural organization of exosome-like extracellular vesicle membranes by [@PMID:30251702]. 
 Glycosylation is a ubiquitous modification that regulates a variety of T cell functions, such as cellular migration, T cell receptor signaling, cell survival, and apoptosis [@PMID:22288421; @PMID:18846099].
@@ -39,7 +40,7 @@ MS-based proteomics approaches are currently the predominant tool for identifyin
 
 #### Protein Structure
 
-Almost all proteins (except for intrinsically disordered proteins[@doi:10.1146/annurev-biochem-072711-164947]) fold into 3D structures either by themselves or assisted through chaperones[@doi:10.1007/s12013-021-00970-5]. 
+Almost all proteins (except for intrinsically disordered proteins[@doi:10.1146/annurev-biochem-072711-164947]) fold into three-dimensional (3D) structures either by themselves or assisted through chaperones[@doi:10.1007/s12013-021-00970-5]. 
 There are four levels relevant to the folding of any protein: 
 
 - Primary structure: 
@@ -54,4 +55,4 @@ The three-dimensional structure of the protein.
 - Quaternary structure: 
 The structure of several protein molecules/subunits in one complex.
 
-Of recent note, the development of AlphaFold, has enabled the high-accuracy three-dimensional structure of all human proteins and many other species enabling the study of protein folding and its relationship to function [@PMID:34265844; @PMID:37732824].
+Of recent note, the development of AlphaFold, has enabled the high-accuracy three-dimensional structural prediction of all human proteins and for proteins of many other species, enabling a more thorough study of protein folding and its relationship to function [@PMID:34265844; @PMID:37732824].