Evolutionary Origin of the αC Helix in Integrins

Integrins are a large family of multidomain α/β cell signaling receptors. Some integrins contain an additional inserted I domain, whose earliest expression appears to be with the chordates, since they are observed in the urochordates Ciona intestinalis (vase tunicate) and Halocynthia roretzi (sea pineapple), but not in integrins of earlier diverging species. The domain-s presence is viewed as a hallmark of integrins of higher metazoans, however in vertebrates, there are clearly three structurally-different classes: integrins without I domains, and two groups of integrins with I domains but separable by the presence or absence of an additional αC helix. For example, the αI domains in collagen-binding integrins from Osteichthyes (bony fish) and all higher vertebrates contain the specific αC helix, whereas the αI domains in non-collagen binding integrins from vertebrates and the αI domains from earlier diverging urochordate integrins, i.e. tunicates, do not. Unfortunately, within the early chordates, there is an evolutionary gap due to extinctions between the tunicates and cartilaginous fish. This, coupled with a knowledge gap due to the lack of complete genomic data from surviving species, means that the origin of collagen-binding αC-containing αI domains remains unknown. Here, we analyzed two available genomes from Callorhinchus milii (ghost shark/elephant shark; Chondrichthyes – cartilaginous fish) and Petromyzon marinus (sea lamprey; Agnathostomata), and several available Expression Sequence Tags from two Chondrichthyes species: Raja erinacea (little skate) and Squalus acanthias (dogfish shark); and Eptatretus burgeri (inshore hagfish; Agnathostomata), which evolutionary reside between the urochordates and osteichthyes. In P. marinus, we observed several fragments coding for the αC-containing αI domain, allowing us to shed more light on the evolution of the collagen-binding integrins.

Authors:

• B. Chouhan
• A. Denesyuk
• J. Heino
• M. S. Johnson
• K. Denessiouk

Keywords:

• Integrin αI domain
• integrin evolution
• collagen binding
• structure
• αC helix

References:

[1] Takada, Y., Ye, X. and Simon, S. (2007) The integrins, Genome Biol 8,
pp. 215.1-215.9.
[2] Luo, B.H., Carman, C.V. and Springer, T.A. (2007) Structural basis of
integrin regulation and signaling, Annu Rev Immunol 25, pp. 619-647.
[3] Arnaout, M.A., Goodman, S.L. and Xiong, J.P. (2007) Structure and
mechanics of integrin-based cell adhesion, Curr Opin Cell Biol 19, pp.
495-507.
[4] Shin, S., Wolgamott, L. and Yoon, S.O. (2012) Integrin trafficking and
tumor progression, Int J Cell Biol 2012, pp. 516789.1-516789.7.
[5] Ulanova, M., Gravelle, S. and Barnes, R. (2009) The role of epithelial
integrin receptors in recognition of pulmonary pathogens, J Innate
Immun 1, pp. 4-17.
[6] Xing, L., Huhtala, M., Pietiäinen, V., Käpylä, J., Vuorinen, K.,
Marjomäki, V., Heino, J., Johnson, M. S., Hyypiä, T. and Cheng, R. H.
(2004) Structural and functional analysis of integrin ╬▒2I domain
interaction with echovirus 1, J Biol Chem 279, pp. 11632-11638.
[7] Jokinen, J., White, D. J., Salmela, M., Huhtala, M., Käpylä, J., Sipilä,
K., Puranen, J. S., Nissinen, L., Kankaanpää, P., Marjomäki, V.,
Hyypiä, T., Johnson, M. S. and Heino, J. (2010) Molecular mechanism
of ╬▒2β1 integrin interaction with human echovirus 1, EMBO J 29, pp.
196-208.
[8] Shimaoka, M. and Springer, T.A. (2003) Therapeutic antagonists and
conformational regulation of integrin function, Nat Rev Drug Discov 2,
pp. 703-716.
[9] Larson, R.S., Corbi, A.L., Berman, L. and Springer, T. (1989) Primary
structure of the leukocyte function-associated molecule-1 alpha subunit:
an integrin with an embedded domain defining a protein superfamily, J
Cell Biol 108, pp. 703-712.
[10] Chouhan, B., Denesyuk, A., Heino, J., Johnson, M. S. and Denessiouk,
K. (2011) Conservation of the human-type integrin beta propeller
domain in bacteria, PLoS One 6, e25069.
[11] Lee, J.O., Rieu, P., Arnaout, M.A. and Liddington, R. (1995) Crystal
structure of the A domain from the alpha subunit of integrin CR3
(CD11b/CD18), Cell 80, pp. 631-638.
[12] Emsley, J., King, S.L., Bergelson, J.M. and Liddington, R.C. (1997)
Crystal structure of the I domain from integrin ╬▒2β1, J Biol Chem 272,
pp. 28512-28517.
[13] Huhtala, M., Heino, J., Casciari, D., de Luice, A. and Johnson M.S.
(2005) Integrin evolution: insights from ascidian and teleost fish
genomes, Matrix Biol 24, pp. 83-95.
[14] Heino, J, Huhtala, M., Kapyla, J. and Johnson M.S. (2009) Evolution of
collagen-based adhesion systems, Int J Biochem Cell Biol 41, pp. 341-
348.
[15] Donoghue, P.C. and Purnell, M.A. (2005) Genome duplication,
extinction and vertebrate evolution, Trends Ecol Evol 20, pp. 312-319.
[16] Venkatesh, B., Kirkness, E.F., Loh, Y.H., Halpern, A.L., Lee, A.P.,
Johnson, J., Dandona, N., Viswanathan, L.D., Tay, A., Venter, J.C.,
Strausberg, R.L. and Brenner, S. (2006) Ancient noncoding elements
conserved in the human genome, Science 314, p. 1892.
[17] Altschul, S.F., Gish, W., Miller, W., Myers, E.W. and Lipman, D.J.
(1990) Basic local alignment search tool, J Mol Biol 215, pp. 403-410.
[18] Ewan, R., Huxley-Jones, J., Mould, A.P., Humphries, M.J., Robertson,
D.L. and Boot-Handford, R.P. (2005) The integrins of the urochordate
Ciona intestinalis provide novel insights into the molecular evolution of
the vertebrate integrin family, BMC Evol Biol 5, pp. 31.1-31.18.
[19] Cole, C., Barber J.D. and Barton, G.J. (2008) The Jpred 3 secondary
structure prediction server, Nucleic Acids Research 36, Web Server
issue W197-W201.
[20] Sen, T.Z., Jernigan, R.L., Garnier, J. and Kloczkowski, A. (2005) GOR
V server for protein secondary structure prediction, Bioinformatics 21,
pp. 2787-2788.
[21] Pollastri, G. and McLysaght, A. (2005) Porter: a new, accurate server
for protein secondary structure prediction, Bioinformatics 21, pp. 1719-
1720.
[22] Rost, B and Sander, C. (1994) Combining evolutionary information and
neural networks to predict protein secondary structure, Proteins 19, pp.
55-72.
[23] McGuffin, L.J., Bryson, K. and Jones, D.T. (2000) The PSIPRED
protein structure prediction server, Bioinformatics 16, pp. 404-405.
[24] Salminen, T., Nymalm, Y., Kankare, J., Käpylä, J., Heino, J. and
Johnson, M.S. (1999) Large-scale purification and preliminary x-ray
analysis of the human integrin ╬▒1I domain, Acta Crystallogr D55, pp.
1365-1367.
[25] Nymalm, Y., Puranen, J.S., Nyholm, T.K.M., Käpylä, J., Kidron, H.,
Pentikäinen, O., Airenne, T.T., Heino, J., Slotte, P., Johnson, M.S. and
Salminen, T.A. (2004) structural changes in ╬▒1 I domain of human
integrin ╬▒1β1, J Biol Chem 279, pp. 7962-7970.
[26] Kamata, T., Liddington, R.C. and Takada, Y. (1999) Interaction
between collagen and the ╬▒2 I-domain of integrin ╬▒2β1. Critical role of
conserved residues in the metal ion-dependent adhesion site (MIDAS)
region, J Biol Chem 274, pp. 32108-32111.
[27] Tulla, M., Huhtala, M., Jäälinoja, J., Käpylä, J., Farndale, R.W., Ala-
Kokko, L., Johnson, M.S. and Heino, J. (2007) Analysis of an ascidian
integrin provides new insight into early evolution of collagen
recognition, FEBS Lett 581, pp. 2434-2440.