Protein complex

A protein complex is an assembly of associated proteins. Its composition specifies component identities and their stoichiometry; variable accessory occupancy and transient partners can make the assembly a molecular population of related forms rather than one fixed object.

A nucleoprotein complex is an assembly containing both nucleic acid and protein components. The nucleic acid can be DNA or RNA, and its spatial arrangement and contacts with the proteins are part of the structure. A mixture that merely contains both kinds of molecule is not automatically one associated complex.

The nucleosome core particle is a concrete DNA–protein example. The1997 structure reported by Karolin Luger and colleagues contains146 base pairs of DNA wrapped around a histone octamer. It shows both protein–protein and protein–DNA contacts. Counting the components and mapping their contacts answer different questions: eight histone molecules do not imply eight identical DNA-binding environments.^[ref]

A bacterial small ribosomal subunit provides an RNA–protein example. Its 16S ribosomal RNA and ribosomal proteins form an organized assembly used in translation. The2000 crystal structure links the RNA/protein arrangement to earlier biochemical observations, showing why the nucleic acid is a structural participant rather than merely something carried inside a protein shell.^[ref]

An experiment must also distinguish association from coincidental presence. Co-purification can suggest a complex, while a resolved structure can identify actual contacts; neither an ingredient list nor a bulk protein measurement alone specifies the architecture.

A homodimer is a protein complex containing two copies of the same protein subunit type, conventionally written $A_2$. A heterodimer instead contains two different types, $AB$. Identical subunit type does not require the copies to occupy identical conformations or environments in every instant of the complex's motion.

Assembly is part of protein quaternary structure, rather than a claim that the two chains have become one longer polypeptide. If each subunit contains 100 amino acid residues, the homodimer contains 200 residues across two chains. Association alone need not add a peptide bond between them.

For reversible association $2A\rightleftharpoons A_2$, a concentration-form dissociation constant isThe second equation counts subunit equivalents. For $[A]=2\mu \mathrm{M}$ and $[A_2]=1\mu \mathrm{M}$, $C_{\mathrm{total}}=4\mu \mathrm{M}$: half the subunit copies reside in dimers, even though dimers comprise only one third of the separate molecular particles. The written $K_d$ uses the usual macroscopic concentration convention.

HIV-1 protease supplies an experimentally important example. Recombinant enzyme had reported molecular masses of approximately 11,000 under denaturing conditions and 22,000 under nondenaturing conditions; chemical crosslinking provided additional evidence consistent with an active two-subunit enzyme. Comparing several measurements was more informative than assigning a homodimer solely from an apparent mass in one assay.^[ref]

In protein chemistry, a heterodimer is an assembly of two different protein subunits, conventionally written $AB$. A homodimer has two copies of the same subunit type, $A_2$. Different types can have similar protein folds and nearly equal molecular masses; “different” refers to molecular identity, not simply size or shape. An $A_2{B}_2$ protein complex contains two types but four chains, so it is not itself a heterodimer.

The alpha/beta tubulin heterodimer is the repeating building block of a microtubule. The alpha and beta protein subunits have similar folds but distinct sequences and nucleotide environments. Their structural relationship was resolved by electron crystallography of zinc-induced tubulin sheets: the 1998 model reached $3.7$ angstrom resolution. This is a concrete example of a two-chain protein quaternary structure, rather than the protein tertiary structure of a single chain.^[ref]

Stoichiometry gives a useful upper bound. If an idealized mixture contains $3\mu \mathrm{mol}$ of $A$ and $2\mu \mathrm{mol}$ of $B$, and only $AB$ can assemble, at most $2\mu \mathrm{mol}$ of heterodimer can form; at least $1\mu \mathrm{mol}$ of $A$ remains outside $AB$. The actual amount also depends on binding equilibrium and experimental conditions: chain counting alone does not guarantee complete association.

A protein subunit is an individual polypeptide component of a protein complex. The number of protein subunits counts chain copies, whereas the number of subunit types counts distinct kinds of chain. An assembly $A_2{B}_2$ has four protein subunits of two types. A protein domain is a region within a chain and need not be a separate protein subunit; the arrangement of several chains belongs to protein quaternary structure.

The alpha/beta tubulin heterodimer illustrates the distinction: it contains two related but different polypeptides, not two domains cut out of one chain. The 1998 electron-crystallographic model resolved the alpha/beta architecture at $3.7$ angstrom resolution, using zinc-induced tubulin sheets.^[ref]

Subunit counting can also become an optical experiment. In total internal reflection fluorescence microscopy, tagged membrane proteins can be observed as isolated fluorescent spots; successive photobleaching steps reveal individual fluorescent tags disappearing. Subunit counting in membrane-bound proteins by Maximilian H. Ulbrich and Ehud Y. Isacoff used this approach on membrane proteins expressed in frog oocytes. For NR1/NR3B receptor assemblies, tagging one component type mainly gave two steps, while tagging both gave four, supporting a two-plus-two arrangement.^[ref]

A count of visible steps need not equal the true number of protein subunits: some tags fail to fluoresce, and two tags may bleach too close together to resolve. The experiment therefore combines step counts with a model of labeling and detection, rather than interpreting every two-step trace as proof of a two-chain protein complex.^[ref]

A vesicle-tethering complex connecting membrane traffic to a selected cell surface. Recruitment to an apical initiation site helps coordinate delivery during epithelial lumen formation.

A cellulosome organizes multiple carbohydrate-degrading enzymes on a scaffold. Local cooperation, substrate attachment and diffusion constraints jointly influence its performance.

ERMES is the yeast ER–mitochondria encounter structure, a contact-associated complex. Synthetic-tether rescue and lipid-conversion assays help distinguish its architectural and functional contributions.