A novel human tectonin protein with multivalent beta-propeller folds interacts with ficolin and binds bacterial LPS
Background Although the human genome database has been completed a decade ago, ~50% of the proteome remains hypothetical as their functions are unknown. The elucidation of the functions of these hypothetical proteins can lead to additional protein pathways and revelation of new cascades. However,...
| Main Authors: | , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2010
|
| Online Access: | http://hdl.handle.net/1721.1/52401 https://orcid.org/0000-0002-5687-6154 |
| _version_ | 1811069930425024512 |
|---|---|
| author | Low, Dianna Hooi Ping Ang, Zhiwei Yuan, Quan Frecer, Vladimir Ho, Bow Chen, Jianzhu Ding, Jeak Ling |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Low, Dianna Hooi Ping Ang, Zhiwei Yuan, Quan Frecer, Vladimir Ho, Bow Chen, Jianzhu Ding, Jeak Ling |
| author_sort | Low, Dianna Hooi Ping |
| collection | MIT |
| description | Background
Although the human genome database has been completed a decade ago, ~50% of the proteome remains hypothetical as their functions are unknown. The elucidation of the functions of these hypothetical proteins can lead to additional protein pathways and revelation of new cascades. However, many of these inferences are limited to proteins with substantial sequence similarity. Of particular interest here is the Tectonin domain-containing family of proteins.
Methodology/Principal Findings
We have identified hTectonin, a hypothetical protein in the human genome database, as a distant ortholog of the limulus galactose binding protein (GBP). Phylogenetic analysis revealed strong evolutionary conservation of hTectonin homologues from parasite to human. By computational analysis, we showed that both the hTectonin and GBP form β-propeller structures with multiple Tectonin domains, each containing β-sheets of 4 strands per β-sheet. hTectonin is present in the human leukocyte cDNA library and immune-related cell lines. It interacts with M-ficolin, a known human complement protein whose ancient homolog, carcinolectin (CL5), is the functional protein partner of GBP during infection. Yeast 2-hybrid assay showed that only the Tectonin domains of hTectonin recognize the fibrinogen-like domain of the M-ficolin. Surface plasmon resonance analysis showed real-time interaction between the Tectonin domains 6 & 11 and bacterial LPS, indicating that despite forming 2 β-propellers with its different Tectonin domains, the hTectonin molecule could precisely employ domains 6 & 11 to recognise bacteria.
Conclusions/Significance
By virtue of a recent finding of another Tectonin protein, leukolectin, in the human leukocyte, and our structure-function analysis of the hypothetical hTectonin, we propose that Tectonin domains of proteins could play a vital role in innate immune defense, and that this function has been conserved over several hundred million years, from invertebrates to vertebrates. Furthermore, the approach we have used could be employed in unraveling the characteristics and functions of other hypothetical proteins in the human proteome. |
| first_indexed | 2024-09-23T08:19:08Z |
| format | Article |
| id | mit-1721.1/52401 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:19:08Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/524012022-09-30T08:59:02Z A novel human tectonin protein with multivalent beta-propeller folds interacts with ficolin and binds bacterial LPS Low, Dianna Hooi Ping Ang, Zhiwei Yuan, Quan Frecer, Vladimir Ho, Bow Chen, Jianzhu Ding, Jeak Ling Massachusetts Institute of Technology. Department of Biology Chen, Jianzhu Chen, Jianzhu Background Although the human genome database has been completed a decade ago, ~50% of the proteome remains hypothetical as their functions are unknown. The elucidation of the functions of these hypothetical proteins can lead to additional protein pathways and revelation of new cascades. However, many of these inferences are limited to proteins with substantial sequence similarity. Of particular interest here is the Tectonin domain-containing family of proteins. Methodology/Principal Findings We have identified hTectonin, a hypothetical protein in the human genome database, as a distant ortholog of the limulus galactose binding protein (GBP). Phylogenetic analysis revealed strong evolutionary conservation of hTectonin homologues from parasite to human. By computational analysis, we showed that both the hTectonin and GBP form β-propeller structures with multiple Tectonin domains, each containing β-sheets of 4 strands per β-sheet. hTectonin is present in the human leukocyte cDNA library and immune-related cell lines. It interacts with M-ficolin, a known human complement protein whose ancient homolog, carcinolectin (CL5), is the functional protein partner of GBP during infection. Yeast 2-hybrid assay showed that only the Tectonin domains of hTectonin recognize the fibrinogen-like domain of the M-ficolin. Surface plasmon resonance analysis showed real-time interaction between the Tectonin domains 6 & 11 and bacterial LPS, indicating that despite forming 2 β-propellers with its different Tectonin domains, the hTectonin molecule could precisely employ domains 6 & 11 to recognise bacteria. Conclusions/Significance By virtue of a recent finding of another Tectonin protein, leukolectin, in the human leukocyte, and our structure-function analysis of the hypothetical hTectonin, we propose that Tectonin domains of proteins could play a vital role in innate immune defense, and that this function has been conserved over several hundred million years, from invertebrates to vertebrates. Furthermore, the approach we have used could be employed in unraveling the characteristics and functions of other hypothetical proteins in the human proteome. 2010-03-08T21:19:58Z 2010-03-08T21:19:58Z 2009-07 2009-06 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/52401 Low, Diana Hooi Ping et al. “A Novel Human Tectonin Protein with Multivalent β-Propeller Folds Interacts with Ficolin and Binds Bacterial LPS.” PLoS ONE 4.7 (2009): e6260. 19606221 https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1371/journal.pone.0006260 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Low, Dianna Hooi Ping Ang, Zhiwei Yuan, Quan Frecer, Vladimir Ho, Bow Chen, Jianzhu Ding, Jeak Ling A novel human tectonin protein with multivalent beta-propeller folds interacts with ficolin and binds bacterial LPS |
| title | A novel human tectonin protein with multivalent beta-propeller folds interacts with ficolin and binds bacterial LPS |
| title_full | A novel human tectonin protein with multivalent beta-propeller folds interacts with ficolin and binds bacterial LPS |
| title_fullStr | A novel human tectonin protein with multivalent beta-propeller folds interacts with ficolin and binds bacterial LPS |
| title_full_unstemmed | A novel human tectonin protein with multivalent beta-propeller folds interacts with ficolin and binds bacterial LPS |
| title_short | A novel human tectonin protein with multivalent beta-propeller folds interacts with ficolin and binds bacterial LPS |
| title_sort | novel human tectonin protein with multivalent beta propeller folds interacts with ficolin and binds bacterial lps |
| url | http://hdl.handle.net/1721.1/52401 https://orcid.org/0000-0002-5687-6154 |
| work_keys_str_mv | AT lowdiannahooiping anovelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT angzhiwei anovelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT yuanquan anovelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT frecervladimir anovelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT hobow anovelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT chenjianzhu anovelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT dingjeakling anovelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT lowdiannahooiping novelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT angzhiwei novelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT yuanquan novelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT frecervladimir novelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT hobow novelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT chenjianzhu novelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps AT dingjeakling novelhumantectoninproteinwithmultivalentbetapropellerfoldsinteractswithficolinandbindsbacteriallps |