MHC class II tetramers can also be made, although these are more difficult to work with practically. Homotetramers and heterotetramers A homotetramer is a protein complex made up of four identical subunits which are associated but not covalently bound. Conversely, a heterotetramer is a 4-subunit complex where one or more subunits differ. Examples of homotetramers include: enzymes like beta-glucuronidase (pictured) export factors such as SecB from Escherichia coli magnesium ion transporters such as CorA. lectins such as Concanavalin A IMPDH and IMPDH2 Examples of heterotetramers include haemoglobin (pictured), the NMDA receptor, some aquaporins, some AMPA receptors, as well as some enzymes. Purification of heterotetramers Ion-exchange chromatography is useful for isolating specific heterotetrameric protein assemblies, allowing purification of specific complexes according to both the number and the position of charged peptide tags. Nickel affinity chromatography may also be employed for heterotetramer purification. Intragenic complementation Multiple copies of a polypeptide encoded by a gene often can form an aggregate referred to as a multimer. When a multimer is formed from polypeptides produced by two different mutant alleles of a particular gene, the mixed multimer may exhibit greater functional activity than the unmixed multimers formed by each of the mutants alone. When a mixed multimer displays increased functionality relative to the unmixed multimers, the phenomenon is referred to as intragenic complementation. In humans, argininosuccinate lyase (ASL) is a homotetrameric enzyme that can undergo intragenic complementation. An ASL disorder in humans can arise from mutations in the ASL gene, particularly mutations that affect the active site of the tetrameric enzyme. ASL disorder is associated with considerable clinical and genetic heterogeneity which is considered to reflect the extensive intragenic complementation occurring among different individual patients. References External links T-cell Group - Cardiff University Immunology Proteins Protein complexes