Protein Classification and Families

Proteins can be classified in various ways based on their structure, function, evolutionary relationships, or biochemical properties. Understanding protein classification systems is important for organizing our knowledge of protein diversity and for predicting the properties of newly discovered proteins. These classification schemes also provide insights into protein evolution and the relationships between structure and function.

Protein Classification and Families

The four major structural classes in SCOP are all-α (proteins composed mainly of α-helices), all-β (proteins composed mainly of β-sheets), α/β (proteins with alternating α-helices and β-strands), and α+β (proteins with segregated α-helical and β-sheet regions). These classes reflect fundamental differences in protein architecture and provide a framework for understanding structural diversity.

Protein folds represent recurring structural motifs that are found in multiple, often unrelated proteins. Common folds include the immunoglobulin fold, the Rossmann fold (found in nucleotide-binding proteins), and the TIM barrel (a common enzyme fold). The existence of common folds suggests that certain structural arrangements are particularly stable or functionally advantageous, leading to their independent evolution or conservation across different protein families.

Functional Classification

Functional classification organizes proteins based on their biological roles and biochemical activities. The Gene Ontology (GO) project provides a standardized vocabulary for describing protein functions across three domains: molecular function (what the protein does), biological process (the larger process the protein contributes to), and cellular component (where the protein is located).

Enzyme classification follows a systematic scheme developed by the International Union of Biochemistry and Molecular Biology (IUBMB). Enzymes are classified into six major classes based on the type of reaction they catalyze: oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Each enzyme is assigned a unique EC (Enzyme Commission) number that precisely identifies its catalytic activity.

Transport proteins can be classified based on their mechanism of action (channels, carriers, or pumps) and the types of molecules they transport. Ion channels are further classified based on their selectivity (sodium, potassium, calcium, etc.) and their gating mechanisms (voltage-gated, ligand-gated, or mechanically-gated). This functional classification is important for understanding physiological processes and for drug development.

Evolutionary Classification and Protein Families

Evolutionary classification groups proteins based on their evolutionary relationships, as inferred from sequence and structural similarities. Proteins that share a common evolutionary origin are said to be homologous, and they are grouped into protein families. Members of a protein family typically share similar structures and functions, though they may have diverged to perform specialized roles in different organisms or cellular contexts.

Protein domains are independently folding units within proteins that often correspond to functional units. Many proteins are composed of multiple domains, and these domains can be shuffled between different proteins during evolution, creating new protein architectures and functions. Domain databases like Pfam and InterPro catalog these recurring structural and functional units and provide tools for identifying domains in newly sequenced proteins.

Orthologous proteins are homologous proteins in different species that typically retain the same function, while paralogous proteins are homologous proteins within the same species that may have similar or divergent functions. Understanding these evolutionary relationships is crucial for transferring functional annotations between species and for predicting the functions of newly discovered proteins.

Membrane Proteins and Specialized Classes

Membrane proteins represent a specialized class of proteins that are adapted for association with or insertion into biological membranes. These proteins can be classified as integral membrane proteins (which span the membrane) or peripheral membrane proteins (which associate with membrane surfaces). Integral membrane proteins often have hydrophobic transmembrane regions that interact with the lipid bilayer.

Transmembrane proteins can be further classified based on the number of times they cross the membrane and their topology. Single-pass transmembrane proteins cross the membrane once, while multi-pass proteins have multiple transmembrane segments. The orientation of these proteins (which end faces which side of the membrane) is crucial for their function and is determined during protein synthesis and insertion.

Intrinsically disordered proteins (IDPs) represent another specialized class that lacks stable secondary and tertiary structure under physiological conditions. These proteins challenge traditional structure-function paradigms and are often involved in signaling, regulation, and protein-protein interactions. IDPs can undergo disorder-to-order transitions upon binding to their targets, allowing for highly specific yet reversible interactions.

Fibrous proteins form another distinct class characterized by elongated, often repetitive structures that provide mechanical support. Examples include collagen (with its triple-helix structure), keratin (with its α-helical coiled-coil structure), and silk fibroin (with its β-sheet structure). These proteins are optimized for mechanical properties rather than catalytic activity and often have unique amino acid compositions that support their structural roles.