6okq

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the SF12 Fab

Structural highlights

6okq is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IGG1_HUMAN Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:20176268, PubMed:17576170).^[1] ^[2] ^[3]

Publication Abstract from PubMed

Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3A cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448gp120 glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development.

Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope.,Schoofs T, Barnes CO, Suh-Toma N, Golijanin J, Schommers P, Gruell H, West AP Jr, Bach F, Lee YE, Nogueira L, Georgiev IS, Bailer RT, Czartoski J, Mascola JR, Seaman MS, McElrath MJ, Doria-Rose NA, Klein F, Nussenzweig MC, Bjorkman PJ Immunity. 2019 May 14. pii: S1074-7613(19)30194-3. doi:, 10.1016/j.immuni.2019.04.014. PMID:31126879^[4]

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

References

↑ Teng G, Papavasiliou FN. Immunoglobulin somatic hypermutation. Annu Rev Genet. 2007;41:107-20. PMID:17576170 doi:http://dx.doi.org/10.1146/annurev.genet.41.110306.130340
↑ Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S41-52. doi:, 10.1016/j.jaci.2009.09.046. PMID:20176268 doi:http://dx.doi.org/10.1016/j.jaci.2009.09.046
↑ McHeyzer-Williams M, Okitsu S, Wang N, McHeyzer-Williams L. Molecular programming of B cell memory. Nat Rev Immunol. 2011 Dec 9;12(1):24-34. doi: 10.1038/nri3128. PMID:22158414 doi:http://dx.doi.org/10.1038/nri3128
↑ Schoofs T, Barnes CO, Suh-Toma N, Golijanin J, Schommers P, Gruell H, West AP Jr, Bach F, Lee YE, Nogueira L, Georgiev IS, Bailer RT, Czartoski J, Mascola JR, Seaman MS, McElrath MJ, Doria-Rose NA, Klein F, Nussenzweig MC, Bjorkman PJ. Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope. Immunity. 2019 May 14. pii: S1074-7613(19)30194-3. doi:, 10.1016/j.immuni.2019.04.014. PMID:31126879 doi:http://dx.doi.org/10.1016/j.immuni.2019.04.014

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/6okq"

Categories: Homo sapiens | Large Structures | Barnes CO | Bjorkman PJ

@@ Line 3: / Line 3: @@
 <StructureSection load='6okq' size='340' side='right'caption='[[6okq]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6okq]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OKQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OKQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6okq]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OKQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OKQ FirstGlance]. <br>
-</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=6okq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6okq OCA], [http://pdbe.org/6okq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6okq RCSB], [http://www.ebi.ac.uk/pdbsum/6okq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6okq ProSAT]</span></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]] 3.2&#8491;</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=6okq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6okq OCA], [https://pdbe.org/6okq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6okq RCSB], [https://www.ebi.ac.uk/pdbsum/6okq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6okq ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/IGG1_HUMAN IGG1_HUMAN] Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:20176268, PubMed:17576170).<ref>PMID:17576170</ref> <ref>PMID:20176268</ref> <ref>PMID:22158414</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Barnes, C O]]
+[[Category: Barnes CO]]
-[[Category: Bjorkman, P J]]
+[[Category: Bjorkman PJ]]
-[[Category: Envelope]]
-[[Category: Fab structure]]
-[[Category: Hiv-1 broadly-neutralizing antibody]]
-[[Category: Immune system]]
-[[Category: Silent face]]

6okq

From Proteopedia

Current revision

Crystal structure of the SF12 Fab

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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