Molecular Machines and Human Disorders


Living cells contain various kinds of molecular machine constructed from protein molecules, sometimes with nucleic acid molecules. They work for free energy conversion, information transfer and the performance of specific physical and chemical processes.

Keywords: ATP synthetase; sliding machine; cargo transport; proteasome; chaperonin; syndromes; neuropathy; cardiomyopathy; deafness; myosin family; troponins


Baracca A, Barogi S, Carelli V, Lenaz G and Solaini G (2000) Catalytic activities of mitochondrial ATP synthase in patients with mitochondrial DNA T8993G mutation in the ATPase 6 gene encoding subunit a. Journal of Biological Chemistry 275: 4177–4182.

Cooper E and Yeh Jan L (1999) Ion channel genes and human neurological disease: recent progress, prospects and challenges. Proceedings of the National Academy of Sciences of the United States of America 96: 4759–4766.

Cramer L (2000) Myosin VI, roles for a minusend‐directed actin motor in cells. Journal of Cell Biology 150: 121–126.

Hartle F (1996) Molecular chaperons in cellular protein folding. Nature 381: 571–580.

Heath K, Campos‐Barros A, Toren A, et al. (2001) Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias; May–Hegglin anomaly and Fechtner, Sebastian. Epstein, and Alport‐like syndromes. American Journal of Human Genetics 69: 1033–1045.

Karibe A and Tobacman LD (2001) Hypertrophic cardiomyopathy caused by a novel alpha‐tropomyosin mutation (V95A) is associated with mild cardiac phenotype, abnormal calcium binding to troponin, abnormal myosin cycling, and poor prognosis. Circulation 103: 65–71.

Kato G (1999) Human genetic diseases of proteolysis. Human Mutation 13: 87–98.

Kinosita K, Yasuda R, Noji H, et al. (1998) FI ATPase: a rotary motor made of a single molecule. Cell 93: 21–24.

Kitamura K, Tokunga M, Iwane A and Yanagida T (1999) A single myosin head moves along an actin filament with regular steps of 5.3 nm. Nature 397: 129–134.

Liu X, Walsh J, Kendrick‐Jones J, et al. (1997) Mutations in the myosin VIIA gene cause non‐syndromic recessive deafness. Nature Genetics 16: 188–190.

May–Hegglin/Fechtner Syndrome Consortium (1997) Mutations in MYH9 result in the May–Hegglin anomaly, and Fechtner and Sebastian syndromes. Nature Genetics 16: 191–193.

Mogensen J and Klausen IC (1999) Alpha‐cardiac actin gene is a novel disease gene in familial hypertrophic cardiomyopathy. Journal of Clinical Investigation 103: 39–43.

Morimoto S, Lu Q, Harada K, et al. (2002) Ca2+‐desensitizing effect of a deletion mutation delta‐K210 in cardiac troponin T that causes familial dilated cardiomyopthy. Proceedings of the National Academy of Sciences of the United States of America 99: 913–918.

Morimoto S, Yanaga F, Minakami R and Ohtsuki I (1998) Ca2+ sensitizing effects of the mutations at Ile‐79 and Arg‐92 of troponin T in hypertrophic cardiomyopathy. American Journal of Physiology 26: 200–207.

Okada Y and Hirokawa N (1999) A processive single headed motor, kinesin superfamily protein KIF1A. Science 283: 1152–1157.

Oosawa F (2000) The loose coupling mechanism in molecular machines of living cells. Genes to Cells 5: 9–16.

Oosawa F and Hayashi S (1986) The loose coupling mechanism in molecular machines of living cells. Advances in Biophysics 22: 151–183.

Poetter K, Jiang H, Hassanzadeh S, et al. (1996) Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Nature Genetics 13: 63–69.

Rayment I, Holden H, Sellers J, Fananapazir L and Epstein N (1995) Structural interpretation of the mutations in the beta‐cardiac myosin that have been implicated in familial hypertrophic cardiomyopathy. Proceedings of the National Academy of Sciences of the United States of America 92: 3864–3868.

Stone D, Slavotinek A, Bouffard G, et al. (2000) Mutation of a gene encoding a putative chaperonin causes McKusick–Kaufman syndrome. Nature Genetics 25: 79–82.

Wang A, Liang Y, Fridell R, et al. (1999) Association of unconventional myosin MYO 15 mutations with human nonsyndromic deafness DFNB3. Science 280: 1447–1449.

Zhao C, Takita J, Tanaka Y, et al. (2001) Charcot–Marie–Tooth disease type 2A caused by mutation in a microtubule motor KIF1B beta. Cell 105: 587–597.

Zwicki P, Voges D and Baumeister W (1999) The proteasome, a macromolecular assembly designed for controlled proteolysis. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences 354: 1501–1511.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Oosawa, Fumio(Sep 2005) Molecular Machines and Human Disorders. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005168]