4k12

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{{STRUCTURE_4k12| PDB=4k12 | SCENE= }}
 
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===Structural Basis for Host Specificity of Factor H Binding by Streptococcus pneumoniae===
 
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==Disease==
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==Structural Basis for Host Specificity of Factor H Binding by Streptococcus pneumoniae==
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[[http://www.uniprot.org/uniprot/CFAH_HUMAN CFAH_HUMAN]] Genetic variations in CFH are associated with basal laminar drusen (BLD) [MIM:[http://omim.org/entry/126700 126700]]; also known as drusen of Bruch membrane or cuticular drusen or grouped early adult-onset drusen. Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. Basal laminar drusen refers to an early adult-onset drusen phenotype that shows a pattern of uniform small, slightly raised yellow subretinal nodules randomly scattered in the macula. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss. Defects in CFH are the cause of complement factor H deficiency (CFHD) [MIM:[http://omim.org/entry/609814 609814]]. A disorder that can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. Laboratory features usually include decreased serum levels of factor H, complement component C3, and a decrease in other terminal complement components, indicating activation of the alternative complement pathway. It is associated with a number of renal diseases with variable clinical presentation and progression, including membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome.<ref>PMID:9312129</ref> <ref>PMID:10803850</ref> <ref>PMID:11170895</ref> <ref>PMID:11170896</ref> <ref>PMID:11158219</ref> <ref>PMID:12020532</ref> <ref>PMID:14978182</ref> <ref>PMID:16612335</ref> Defects in CFH are a cause of susceptibility to hemolytic uremic syndrome atypical type 1 (AHUS1) [MIM:[http://omim.org/entry/235400 235400]]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:14978182</ref> <ref>PMID:9551389</ref> <ref>PMID:10577907</ref> <ref>PMID:10762557</ref> <ref>PMID:11851332</ref> <ref>PMID:14583443</ref> <ref>PMID:12960213</ref> <ref>PMID:20513133</ref> Genetic variation in CFH is associated with age-related macular degeneration type 4 (ARMD4) [MIM:[http://omim.org/entry/610698 610698]]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:22019782</ref>
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<StructureSection load='4k12' size='340' side='right'caption='[[4k12]], [[Resolution|resolution]] 1.08&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4k12]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K12 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.079&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4k12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k12 OCA], [https://pdbe.org/4k12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k12 RCSB], [https://www.ebi.ac.uk/pdbsum/4k12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k12 ProSAT]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Many human pathogens have strict host specificity, which affects not only their epidemiology but also development of animal models and vaccines. Complement factor H (FH) is recruited to pneumococcal cell surface in a human-specific manner via the N-terminal domain of the pneumococcal protein virulence factor CbpA (CbpAN). FH recruitment enables Streptococcus pneumoniae to evade surveillance by human complement system and contributes to pneumococcal host specificity. The molecular determinants of host specificity of complement evasion are unknown. Here we show that a single human FH domain is sufficient for tight binding of CbpAN, present the crystal structure of the complex, and identify the critical structural determinants for host-specific FH recruitment. The results offer new approaches to development of better animal models for pneumococcal infection and redesign of the virulence factor for pneumococcal vaccine development, and reveal how FH recruitment can serve as a mechanism for both pneumococcal complement evasion and adherence.
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==Function==
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Structural Determinants of Host Specificity of Complement Factor H Recruitment by Streptococcus pneumoniae.,Achila D, Liu A, Banerjee R, Li Y, Martinez-Hackert E, Zhang JR, Yan H Biochem J. 2014 Oct 21. PMID:25330773<ref>PMID:25330773</ref>
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[[http://www.uniprot.org/uniprot/CFAH_HUMAN CFAH_HUMAN]] Factor H functions as a cofactor in the inactivation of C3b by factor I and also increases the rate of dissociation of the C3bBb complex (C3 convertase) and the (C3b)NBB complex (C5 convertase) in the alternative complement pathway.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4k12]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K12 OCA].
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</div>
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<div class="pdbe-citations 4k12" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<references group="xtra"/><references/>
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*[[Complement factor 3D structures|Complement factor 3D structures]]
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[[Category: Achila, D.]]
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== References ==
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[[Category: Banerjee, R.]]
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<references/>
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[[Category: Li, Y.]]
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__TOC__
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[[Category: Liu, A.]]
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</StructureSection>
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[[Category: Martinez-Hackert, E.]]
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[[Category: Homo sapiens]]
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[[Category: Yan, H.]]
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[[Category: Large Structures]]
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[[Category: Complement-binding complex]]
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[[Category: Streptococcus pneumoniae]]
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[[Category: Immune system-choline binding protein complex]]
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[[Category: Achila D]]
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[[Category: Protein-protein complex]]
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[[Category: Banerjee R]]
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[[Category: Li Y]]
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[[Category: Liu A]]
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[[Category: Martinez-Hackert E]]
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[[Category: Yan H]]

Current revision

Structural Basis for Host Specificity of Factor H Binding by Streptococcus pneumoniae

PDB ID 4k12

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