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5o1r

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human Fab 5H2 bound to NHBA-C3 from Neisseria meningitidis serogroup B

Structural highlights

5o1r is a 6 chain structure with sequence from Homo sapiens and Neisseria meningitidis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.86Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NHBA_NEIME A major human immunogenic protein detected in patients recovering from meningitidis, where it induces bactericidal antibodies (PubMed:30133484) (By similarity). Binds human cells, heparin and heparan sulfate proteoglycan in vitro via the Arg-rich motif. Heparin-binding to this protein protects bacteria against killing by bactericidal antibodies (serum killing). The bacteria binds a number of human extracellular sialyated and/or sulfated glycans via this protein, including chondroitin sulfate, heparin and ganglioside GT3. Binds DNA non-specifically (By similarity).[UniProtKB:Q7DD37]^[1] May play a role in extracellular-DNA (eDNA) mediated biofilm formation. When NHBA is not processed by NalP there is an increase in biofilm formation (PubMed:23163582). Lack of processing may lead to an increase in positively charged, NHBA- and IgA-derived DNA-binding peptides on the cell surface, resulting in increased DNA-binding peptides and increased biofilm formation (Probable).^[2] ^[3]

Publication Abstract from PubMed

Neisserial heparin binding antigen (NHBA) is one of three main recombinant protein antigens in 4CMenB, a vaccine for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroup B. NHBA is a surface-exposed lipoprotein composed of a predicted disordered N-terminal region, an arginine-rich region that binds heparin, and a C-terminal domain that folds as an anti-parallel beta-barrel and that upon release after cleavage by human proteases alters endothelial permeability. NHBA induces bactericidal antibodies in humans, and NHBA-specific antibodies elicited by the 4CMenB vaccine contribute to serum bactericidal activity, the correlate of protection. To better understand the structural bases of the human antibody response to 4CMenB vaccination and to inform antigen design, we used X-ray crystallography to elucidate the structures of two C-terminal fragments of NHBA, either alone or in complex with the Fab derived from the vaccine-elicited human monoclonal antibody 5H2, and the structure of the unbound Fab 5H2. The structures reveal details on the interaction between an N-terminal beta-hairpin fragment and the beta-barrel, and explain how NHBA is capable of generating cross-reactive antibodies through an extensive conserved conformational epitope that covers the entire C-terminal face of the beta-barrel. By providing new structural information on a vaccine antigen and on the human immune response to vaccination, these results deepen our molecular understanding of 4CMenB, and might also aid future vaccine design projects.

Structures of NHBA elucidate a broadly conserved epitope identified by a vaccine induced antibody.,Maritan M, Veggi D, Cozzi R, Dello Iacono L, Bartolini E, Lo Surdo P, Maruggi G, Spraggon G, Bottomley MJ, Malito E PLoS One. 2018 Aug 22;13(8):e0201922. doi: 10.1371/journal.pone.0201922., eCollection 2018. PMID:30133484^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Maritan M, Veggi D, Cozzi R, Dello Iacono L, Bartolini E, Lo Surdo P, Maruggi G, Spraggon G, Bottomley MJ, Malito E. Structures of NHBA elucidate a broadly conserved epitope identified by a vaccine induced antibody. PLoS One. 2018 Aug 22;13(8):e0201922. doi: 10.1371/journal.pone.0201922., eCollection 2018. PMID:30133484 doi:http://dx.doi.org/10.1371/journal.pone.0201922
↑ Arenas J, Nijland R, Rodriguez FJ, Bosma TN, Tommassen J. Involvement of three meningococcal surface-exposed proteins, the heparin-binding protein NhbA, the α-peptide of IgA protease and the autotransporter protease NalP, in initiation of biofilm formation. Mol Microbiol. 2013 Jan;87(2):254-68. PMID:23163582 doi:10.1111/mmi.12097
↑ Arenas J, Nijland R, Rodriguez FJ, Bosma TN, Tommassen J. Involvement of three meningococcal surface-exposed proteins, the heparin-binding protein NhbA, the α-peptide of IgA protease and the autotransporter protease NalP, in initiation of biofilm formation. Mol Microbiol. 2013 Jan;87(2):254-68. PMID:23163582 doi:10.1111/mmi.12097
↑ Maritan M, Veggi D, Cozzi R, Dello Iacono L, Bartolini E, Lo Surdo P, Maruggi G, Spraggon G, Bottomley MJ, Malito E. Structures of NHBA elucidate a broadly conserved epitope identified by a vaccine induced antibody. PLoS One. 2018 Aug 22;13(8):e0201922. doi: 10.1371/journal.pone.0201922., eCollection 2018. PMID:30133484 doi:http://dx.doi.org/10.1371/journal.pone.0201922

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5o1r"

Categories: Homo sapiens | Large Structures | Neisseria meningitidis | Malito E | Maritan M

@@ Line 1: / Line 1: @@
 ==human Fab 5H2 bound to NHBA-C3 from Neisseria meningitidis serogroup B==
-<StructureSection load='5o1r' size='340' side='right' caption='[[5o1r]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
+<StructureSection load='5o1r' size='340' side='right'caption='[[5o1r]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5o1r]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/"diplokokkus_intracellularis_meningitidis"_(sic)_weichselbaum_1887 "diplokokkus intracellularis meningitidis" (sic) weichselbaum 1887] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O1R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O1R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5o1r]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Neisseria_meningitidis Neisseria meningitidis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O1R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O1R FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.86&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gna2132, nhba ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=487 "Diplokokkus intracellularis meningitidis" (sic) Weichselbaum 1887]), IGH@ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5o1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o1r OCA], [http://pdbe.org/5o1r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o1r RCSB], [http://www.ebi.ac.uk/pdbsum/5o1r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o1r ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5o1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o1r OCA], [https://pdbe.org/5o1r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o1r RCSB], [https://www.ebi.ac.uk/pdbsum/5o1r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o1r ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/NHBA_NEIME NHBA_NEIME] A major human immunogenic protein detected in patients recovering from meningitidis, where it induces bactericidal antibodies (PubMed:30133484) (By similarity). Binds human cells, heparin and heparan sulfate proteoglycan in vitro via the Arg-rich motif. Heparin-binding to this protein protects bacteria against killing by bactericidal antibodies (serum killing). The bacteria binds a number of human extracellular sialyated and/or sulfated glycans via this protein, including chondroitin sulfate, heparin and ganglioside GT3. Binds DNA non-specifically (By similarity).[UniProtKB:Q7DD37]<ref>PMID:30133484</ref>   May play a role in extracellular-DNA (eDNA) mediated biofilm formation. When NHBA is not processed by NalP there is an increase in biofilm formation (PubMed:23163582). Lack of processing may lead to an increase in positively charged, NHBA- and IgA-derived DNA-binding peptides on the cell surface, resulting in increased DNA-binding peptides and increased biofilm formation (Probable).<ref>PMID:23163582</ref> <ref>PMID:23163582</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Malito, E]]
+[[Category: Large Structures]]
-[[Category: Maritan, M]]
+[[Category: Neisseria meningitidis]]
-[[Category: Immune system]]
+[[Category: Malito E]]
+[[Category: Maritan M]]

5o1r

From Proteopedia

Current revision

human Fab 5H2 bound to NHBA-C3 from Neisseria meningitidis serogroup B

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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