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A heterotrimer is a protein trimer containing more than one type of protein subunit. It may have composition $A_{2}B$ or $ABC$, for example; the total number of subunits is three in either case. This distinguishes it from a homotrimer, whose three subunits have the same type.

A heterotrimeric G protein illustrates the $ABC$ arrangement, with distinct $\alpha$, $\beta$ and $\gamma$ subunits. A structural inhibitor study crystallized an engineered $\alpha \beta \gamma$ complex and separately measured nucleotide binding and release. Such experiments distinguish the composition of the assembled complex from the chemical activity of one of its components.^[ref]

For an original assembly bound, start with $3\mu \mathrm{M}$ of $A$, $4\mu \mathrm{M}$ of $B$ and $1\mu \mathrm{M}$ of $C$, allowing only $ABC$ complexes. At most $1\mu \mathrm{M}$ complexes can form, leaving at least $2\mu \mathrm{M}$ of $A$ and $3\mu \mathrm{M}$ of $B$ outside them. Adding more $A$ alone cannot overcome the shortage of $C$. Actual assembly may be lower because of incomplete binding or competing complexes.

A homotrimer is a protein trimer containing three copies of the same protein subunit type. “Homo” specifies composition; “trimer” specifies a total of three subunits. A homotrimer need not have perfectly identical instantaneous conformations or ligand occupancies at all three copies.

Polynucleotide phosphorylase provides a functional example. Its three repeated subunits form a ring around the polynucleotide phosphorylase central channel. Cryo-electron microscopy of the mycobacterial enzyme resolved that ring and RNA near a catalytic site, connecting an oligomeric structure with an RNA-processing mechanism.^[ref]

For an original conservation example, let $A$ be an unassembled chain and $A_3$ the assembled homotrimer, with no other forms present:A total chain concentration of $6\mu \mathrm{M}$ can yield at most $2\mu \mathrm{M}$ trimers. If half the chains remain unassembled, only $1\mu \mathrm{M}$ trimers form. Reporting concentration in chains or in complexes therefore changes the numerical value even for the same preparation.

A protein trimer is an assembly of three protein subunits. A homotrimer contains three copies of the same subunit type; a heterotrimer contains different subunit types. Subunit count describes the assembly, while the number of different sequences describes its composition.

For an original mass example, three identical chains of molar mass $M$ form an ideal complex of molar mass $3M$, ignoring modifications and bound ligands. Chains of $25\mathrm{kDa}$ would therefore give $75\mathrm{kDa}$. A heterotrimer made from chains of 20, 25 and 30 kDa has the same total mass. Measuring total mass alone cannot distinguish those two stipulated compositions.

Polynucleotide phosphorylase illustrates why trimerization can matter mechanistically. Its three-subunit ring forms a polynucleotide phosphorylase central channel and positions catalytic regions around the assembly. The original structural study determined that arrangement by X-ray crystallography.^[ref]

Three subunits need not always form a ring or an exactly symmetric structure. Different interfaces, bound ligands and conformational changes can distinguish the subunits even when their sequences match. An observed trimer is therefore a starting point for explaining function, not a complete description of every molecular interaction.