1ywm
From Proteopedia
(New page: 200px<br /><applet load="1ywm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ywm, resolution 1.86Å" /> '''Crystal structure of...) |
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| - | [[Image:1ywm.gif|left|200px]]<br /><applet load="1ywm" size=" | + | [[Image:1ywm.gif|left|200px]]<br /><applet load="1ywm" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ywm, resolution 1.86Å" /> | caption="1ywm, resolution 1.86Å" /> | ||
'''Crystal structure of the N-terminal domain of group B Streptococcus alpha C protein'''<br /> | '''Crystal structure of the N-terminal domain of group B Streptococcus alpha C protein'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Group B Streptococcus (GBS) is the leading cause of bacterial pneumonia, sepsis, and meningitis among neonates and an important cause of morbidity | + | Group B Streptococcus (GBS) is the leading cause of bacterial pneumonia, sepsis, and meningitis among neonates and an important cause of morbidity among pregnant women and immunocompromised adults. Invasive diseases due to GBS are attributed to the ability of the pathogen to translocate across human epithelial surfaces. The alpha C protein (ACP) has been identified as an invasin that plays a role in internalization and translocation of GBS across epithelial cells. The soluble N-terminal domain of ACP (NtACP) blocks the internalization of GBS. We determined the 1.86-A resolution crystal structure of NtACP comprising residues Ser(52) through Leu(225) of the full-length ACP. NtACP has two domains, an N-terminal beta-sandwich and a C-terminal three-helix bundle. Structural and topological alignments reveal that the beta-sandwich shares structural elements with the type III fibronectin fold (FnIII), but includes structural elaborations that make it unique. We have identified a potential integrin-binding motif consisting of Lys-Thr-Asp(146), Arg(110), and Asp(118). A similar arrangement of charged residues has been described in other invasins. ACP shows a heparin binding activity that requires NtACP. We propose a possible heparin-binding site, including one surface of the three-helix bundle, and nearby portions of the sandwich and repeat domains. We have validated this prediction using assays of the heparin binding and cell-adhesion properties of engineered fragments of ACP. This is the first crystal structure of a member of the highly conserved Gram-positive surface alpha-like protein family, and it will enable the internalization mechanism of GBS to be dissected at the atomic level. |
==About this Structure== | ==About this Structure== | ||
| - | 1YWM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_agalactiae Streptococcus agalactiae] with DTU and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1YWM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_agalactiae Streptococcus agalactiae] with <scene name='pdbligand=DTU:'>DTU</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YWM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Streptococcus agalactiae]] | [[Category: Streptococcus agalactiae]] | ||
| - | [[Category: Auperin, T | + | [[Category: Auperin, T C.]] |
| - | [[Category: Baron, M | + | [[Category: Baron, M J.]] |
| - | [[Category: Bolduc, G | + | [[Category: Bolduc, G R.]] |
| - | [[Category: Filman, D | + | [[Category: Filman, D J.]] |
[[Category: Heroux, A.]] | [[Category: Heroux, A.]] | ||
| - | [[Category: Hogle, J | + | [[Category: Hogle, J M.]] |
| - | [[Category: Madoff, L | + | [[Category: Madoff, L C.]] |
[[Category: DTU]] | [[Category: DTU]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
| Line 26: | Line 26: | ||
[[Category: fibronectin fold]] | [[Category: fibronectin fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:09:55 2008'' |
Revision as of 14:09, 21 February 2008
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Crystal structure of the N-terminal domain of group B Streptococcus alpha C protein
Overview
Group B Streptococcus (GBS) is the leading cause of bacterial pneumonia, sepsis, and meningitis among neonates and an important cause of morbidity among pregnant women and immunocompromised adults. Invasive diseases due to GBS are attributed to the ability of the pathogen to translocate across human epithelial surfaces. The alpha C protein (ACP) has been identified as an invasin that plays a role in internalization and translocation of GBS across epithelial cells. The soluble N-terminal domain of ACP (NtACP) blocks the internalization of GBS. We determined the 1.86-A resolution crystal structure of NtACP comprising residues Ser(52) through Leu(225) of the full-length ACP. NtACP has two domains, an N-terminal beta-sandwich and a C-terminal three-helix bundle. Structural and topological alignments reveal that the beta-sandwich shares structural elements with the type III fibronectin fold (FnIII), but includes structural elaborations that make it unique. We have identified a potential integrin-binding motif consisting of Lys-Thr-Asp(146), Arg(110), and Asp(118). A similar arrangement of charged residues has been described in other invasins. ACP shows a heparin binding activity that requires NtACP. We propose a possible heparin-binding site, including one surface of the three-helix bundle, and nearby portions of the sandwich and repeat domains. We have validated this prediction using assays of the heparin binding and cell-adhesion properties of engineered fragments of ACP. This is the first crystal structure of a member of the highly conserved Gram-positive surface alpha-like protein family, and it will enable the internalization mechanism of GBS to be dissected at the atomic level.
About this Structure
1YWM is a Single protein structure of sequence from Streptococcus agalactiae with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of the N-terminal domain of the group B streptococcus alpha C protein., Auperin TC, Bolduc GR, Baron MJ, Heroux A, Filman DJ, Madoff LC, Hogle JM, J Biol Chem. 2005 May 6;280(18):18245-52. Epub 2005 Mar 6. PMID:15753100
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