The rhomboid protease family: a decade of progress on function and mechanism

Genome Biol. 2011 Oct 27;12(10):231. doi: 10.1186/gb-2011-12-10-231.

Abstract

Rhomboid proteases are the largest family of enzymes that hydrolyze peptide bonds within the cell membrane. Although discovered to be serine proteases only a decade ago, rhomboid proteases are already considered to be the best understood intramembrane proteases. The presence of rhomboid proteins in all domains of life emphasizes their importance but makes their evolutionary history difficult to chart with confidence. Phylogenetics nevertheless offers three guiding principles for interpreting rhomboid function. The near ubiquity of rhomboid proteases across evolution suggests broad, organizational roles that are not directly essential for cell survival. Functions have been deciphered in only about a dozen organisms and fall into four general categories: initiating cell signaling in animals, facilitating bacterial quorum sensing, regulating mitochondrial homeostasis, and dismantling adhesion complexes of parasitic protozoa. Although in no organism has the full complement of rhomboid function yet been elucidated, links to devastating human disease are emerging rapidly, including to Parkinson's disease, type II diabetes, cancer, and bacterial and malaria infection. Rhomboid proteases are unlike most proteolytic enzymes, because they are membrane-immersed; understanding how the membrane immersion affects their function remains a key challenge.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Membrane / chemistry
  • Cell Membrane / enzymology
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / classification
  • DNA-Binding Proteins / genetics
  • Drosophila / chemistry
  • Drosophila / enzymology*
  • Drosophila / genetics
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Endopeptidases / chemistry*
  • Endopeptidases / classification
  • Endopeptidases / genetics
  • Enzyme Activation
  • Epidermal Growth Factor / chemistry
  • Epidermal Growth Factor / genetics
  • Escherichia coli / chemistry
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / classification
  • Escherichia coli Proteins / genetics
  • Homeostasis
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / classification
  • Membrane Proteins / genetics
  • Mitochondria / chemistry
  • Mitochondria / genetics
  • Phylogeny
  • Proteolysis
  • Quorum Sensing
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Escherichia coli Proteins
  • GlpG protein, E coli
  • Membrane Proteins
  • spi protein, Drosophila
  • Epidermal Growth Factor
  • Endopeptidases