Editing Protein complex (section)

==Homomultimeric and heteromultimeric proteins==
The subunits of a multimeric protein may be identical as in a homomultimeric (homooligomeric) protein or different as in a heteromultimeric protein. Many soluble and membrane proteins form homomultimeric complexes in a cell, majority of proteins in the [[Protein Data Bank]] are homomultimeric.<ref name="pmid21572178">{{cite journal |vauthors=Hashimoto K, Nishi H, Bryant S, Panchenko AR | title = Caught in self-interaction: evolutionary and functional mechanisms of protein homooligomerization | journal = Phys Biol | volume = 8 | issue = 3 | pages = 035007 |date=June 2011 | pmid = 21572178 | pmc = 3148176 | doi = 10.1088/1478-3975/8/3/035007 | bibcode = 2011PhBio...8c5007H }}</ref> Homooligomers are responsible for the diversity and specificity of many pathways, may mediate and regulate gene expression, activity of enzymes, ion channels, receptors, and cell adhesion processes.

The [[voltage-gated potassium channels]] in the plasma membrane of a neuron are heteromultimeric proteins composed of four of forty known alpha subunits. Subunits must be of the same subfamily to form the multimeric protein channel. The tertiary structure of the channel allows ions to flow through the hydrophobic plasma membrane. [[Connexon]]s are an example of a homomultimeric protein composed of six identical [[connexin]]s. A cluster of connexons forms the gap-junction in two neurons that transmit signals through an [[electrical synapse]].

===Intragenic complementation===

When multiple copies of a polypeptide encoded by a [[gene]] form a complex, this protein structure is referred to as a multimer. When a multimer is formed from polypeptides produced by two different [[mutant]] [[allele]]s of a particular gene, the mixed multimer may exhibit greater functional activity than the unmixed multimers formed by each of the mutants alone. In such a case, the phenomenon is referred to as [[complementation (genetics)#Intragenic complementation|intragenic complementation]] (also called inter-allelic complementation). Intragenic complementation has been demonstrated in many different genes in a variety of organisms including the fungi ''[[Neurospora crassa]]'', ''[[Saccharomyces cerevisiae]]'' and ''[[Schizosaccharomyces pombe]]''; the bacterium ''[[Salmonella]] typhimurium''; the virus [[Escherichia virus T4|bacteriophage T4]],<ref>{{cite journal |last1=Bernstein |first1=H |last2=Edgar |first2=RS |last3=Denhardt |first3=GH |title=Intragenic Complementation among Temperature Sensitive Mutants of Bacteriophage T4D |journal=Genetics |date=June 1965 |volume=51 |issue=6 |pages=987–1002 |doi=10.1093/genetics/51.6.987 |pmid=14337770 |pmc=1210828}}</ref> an RNA virus<ref>Smallwood S, Cevik B, Moyer SA. Intragenic complementation and oligomerization of the L subunit of the sendai virus RNA polymerase. Virology. 2002;304(2):235-245. {{doi|10.1006/viro.2002.1720}}</ref> and humans.<ref>Rodríguez-Pombo P, Pérez-Cerdá C, Pérez B, Desviat LR, Sánchez-Pulido L, Ugarte M. Towards a model to explain the intragenic complementation in the heteromultimeric protein propionyl-CoA carboxylase. Biochim Biophys Acta. 2005;1740(3):489-498. {{doi|10.1016/j.bbadis.2004.10.009}}</ref> In such studies, numerous [[mutation]]s defective in the same gene were often isolated and mapped in a linear order on the basis of [[genetic recombination|recombination]] frequencies to form a [[gene mapping|genetic map]] of the gene. Separately, the mutants were tested in pairwise combinations to measure complementation. An analysis of the results from such studies led to the conclusion that intragenic complementation, in general, arises from the interaction of differently defective polypeptide monomers to form a multimer.<ref>Crick FH, Orgel LE.  The theory of inter-allelic complementation. J Mol Biol. 1964 Jan;8:161-5. {{doi|10.1016/s0022-2836(64)80156-x}}. PMID 14149958</ref> Genes that encode multimer-forming polypeptides appear to be common. One interpretation of the data is that polypeptide monomers are often aligned in the multimer in such a way that mutant polypeptides defective at nearby sites in the genetic map tend to form a mixed multimer that functions poorly, whereas mutant polypeptides defective at distant sites tend to form a mixed multimer that functions more effectively. The intermolecular forces likely responsible for self-recognition and multimer formation were discussed by Jehle.<ref>Jehle H. Intermolecular forces and biological specificity.  Proc Natl Acad Sci U S A. 1963;50(3):516-524. {{doi|10.1073/pnas.50.3.516}}</ref>