Potential Title for subsection: Evolution of Function edit
I will be editing the mechanism, evolution, and history portions of this article.
Edit Mechanism section for biophysical appropriateness section
Mechanism:
UCP1 is very similar to the ATP/ADP Carrier protein, or Adenine Nucleotide Translocator (ANT)[1]. The proposed alternating access model for UCP1 is shown to the left based on the similar ANT mechanism[2]. The substrate comes in to the half open UCP1 protein from the cytoplasmic side of the membrane, the protein closes the cytoplasmic side so the substrate is enclosed in the protein, and then the matrix side of the protein opens, allowing the substrate to be released into the mitochondrial matrix. The opening and closing of the protein is accomplished by the tightening and loosening of salt bridges at the membrane surface of the protein. Substantiation for this modelling of UCP1 on ANT is found in the many conserved residues between the two proteins that are actively involved in the transportation of substrate across the membrane. Both proteins are integral membrane proteins, localized to the inner mitochondrial membrane, and they have a similar pattern of salt bridges, proline residues, and hydrophobic or aromatic amino acids that can close or open when in the cytoplasmic or matrix state.[1]
Evolution edit
UCP1 is expressed in brown adipose tissue, which is functionally found only in eutherians. The UCP1, or thermogenin, gene likely arose in an ancestor of modern vertebrates, but did not initially allow for our vertebrate ancestor to use non-shivering thermogenesis for warmth. It wasn't until heat generation was adaptively selected for in placental mammal descendants of this common ancestor that UCP1 evolved its current function in brown adipose tissue to provide additional warmth[3]. Recent discoveries of non-heat-generating orthologues of UCP1 in fish and marsupials, other descendants of the ancestor of modern vertebrates, show that this gene was passed on to all modern vertebrates, but aside from placental mammals, none have heat producing capability[4]. This further suggests that UCP1 had a different original pupose and in fact phylogenetic and sequence analyses indicate that UCP1 is likely a mutated form of a dicarboxylate carrier protein that adapted for thermogenesis in placental mammals[5].
History: Researchers in the 1960's investigating brown adipose tissue, found that in addition to producing more heat than typical of other tissues, brown adipose tissue actually seemed to short circuit, or uncouple, respiration coupling. UCP1 was later purified for the first time in 1980[6].
https://pdfs.semanticscholar.org/4696/d06ee1e66c8c9fb7f7c87d54a3955e01ab9f.pdf
https://www.ncbi.nlm.nih.gov/pubmed/9914821
Molecular evolution of UCP1 and the evolutionary history of mammalian non-shivering thermogenesis
A history of the first uncoupling protein, UCP1. (DOI: 10.1023/a:1005436121005)
Brown adipose tissue: function and physiological significance. (DOI: 10.1152/physrev.00015.2003)
Adaptive evolution of the uncoupling protein 1 gene contributed to the acquisition of novel nonshivering thermogenesis in ancestral eutherian mammals. (DOI: 10.1016/j.gene.2007.10.018)
An ancient look at UCP1. (DOI: 10.1016/j.bbabio.2008.03.006)
References edit
- ^ a b Crichton, Paul G.; Lee, Yang; Kunji, Edmund R. S. (2017-03-01). "The molecular features of uncoupling protein 1 support a conventional mitochondrial carrier-like mechanism". Biochimie. UCP1: 40 years and beyond. 134: 35–50. doi:10.1016/j.biochi.2016.12.016. ISSN 0300-9084.
- ^ Ryan, Renae M.; Vandenberg, Robert J. (2016-03-01). "Elevating the alternating-access model". Nature Structural & Molecular Biology. 23 (3): 187–189. doi:10.1038/nsmb.3179. ISSN 1545-9985.
- ^ Klingenspor, Martin; Fromme, Tobias; Hughes, David A.; Manzke, Lars; Polymeropoulos, Elias; Riemann, Tobias; Trzcionka, Magdalene; Hirschberg, Verena; Jastroch, Martin (2008-07-01). "An ancient look at UCP1". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 15th European Bioenergetics Conference 2008. 1777 (7): 637–641. doi:10.1016/j.bbabio.2008.03.006. ISSN 0005-2728.
- ^ Saito, Shigeru; Saito, Claire Tanaka; Shingai, Ryuzo (2008-01-31). "Adaptive evolution of the uncoupling protein 1 gene contributed to the acquisition of novel nonshivering thermogenesis in ancestral eutherian mammals". Gene. 408 (1): 37–44. doi:10.1016/j.gene.2007.10.018. ISSN 0378-1119.
- ^ Robinson, Alan J.; Overy, Catherine; Kunji, Edmund R. S. (2008-11-18). "The mechanism of transport by mitochondrial carriers based on analysis of symmetry". Proceedings of the National Academy of Sciences. 105 (46): 17766–17771. doi:10.1073/pnas.0809580105. ISSN 0027-8424. PMID 19001266.
- ^ Ricquier, Daniel (2017-03-01). "UCP1, the mitochondrial uncoupling protein of brown adipocyte: A personal contribution and a historical perspective". Biochimie. UCP1: 40 years and beyond. 134: 3–8. doi:10.1016/j.biochi.2016.10.018. ISSN 0300-9084.
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