4pgj: Difference between revisions
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==Human heavy-chain domain antibody in complex with hen egg-white lysozyme== | ==Human heavy-chain domain antibody in complex with hen egg-white lysozyme== | ||
<StructureSection load='4pgj' size='340' side='right' caption='[[4pgj]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='4pgj' size='340' side='right'caption='[[4pgj]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4pgj]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4pgj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PGJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PGJ FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4pgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pgj OCA], [https://pdbe.org/4pgj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pgj RCSB], [https://www.ebi.ac.uk/pdbsum/4pgj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pgj ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/LYSC_CHICK LYSC_CHICK] Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activity against M.luteus.<ref>PMID:22044478</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human VH single domains represent a promising class of antibody fragments with applications as therapeutic modalities. Unfortunately, isolated human VH domains also generally display poor biophysical properties and a propensity to aggregate. This has encouraged the development of non-human antibody domains as alternative means of antigen recognition and, in particular, camelid (VHH) domains. Naturally devoid of light chain partners, these domains are characterized by favourable biophysical properties and propensity for cleft binding, a highly desirable characteristic, allowing the targeting of cryptic epitopes. In contrast, previously reported structures of human VH single domains had failed to recapitulate this property. Here we report the engineering and characterization of phage display libraries of stable human VH domains, and the selection of binders against a diverse set of antigens. Unlike "camelized" human domains, the domains do not rely on potentially immunogenic framework mutations and maintain the structure of the VH/VL interface. Structure determination in complex with hen egg-white lysozyme revealed an extended VH binding interface, with complementarity determining region 3 (CDR3) deeply penetrating into the active site cleft, highly reminiscent to what has been observed for camelid domains. Taken together, our results demonstrate that fully human VH domains can be constructed that are not only stable and well-expressed, but also rival the cleft binding properties of camelid antibodies. | |||
Fully human VH single domains that rival the stability and cleft recognition of camelid antibodies.,Rouet R, Dudgeon K, Christie M, Langley D, Christ D J Biol Chem. 2015 Mar 3. pii: jbc.M114.614842. PMID:25737448<ref>PMID:25737448</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4pgj" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Lysozyme 3D structures|Lysozyme 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Gallus gallus]] | [[Category: Gallus gallus]] | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Christ D]] | ||
[[Category: | [[Category: Langley DB]] | ||
[[Category: | [[Category: Rouet R]] | ||
Latest revision as of 03:43, 28 December 2023
Human heavy-chain domain antibody in complex with hen egg-white lysozymeHuman heavy-chain domain antibody in complex with hen egg-white lysozyme
Structural highlights
FunctionLYSC_CHICK Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activity against M.luteus.[1] Publication Abstract from PubMedHuman VH single domains represent a promising class of antibody fragments with applications as therapeutic modalities. Unfortunately, isolated human VH domains also generally display poor biophysical properties and a propensity to aggregate. This has encouraged the development of non-human antibody domains as alternative means of antigen recognition and, in particular, camelid (VHH) domains. Naturally devoid of light chain partners, these domains are characterized by favourable biophysical properties and propensity for cleft binding, a highly desirable characteristic, allowing the targeting of cryptic epitopes. In contrast, previously reported structures of human VH single domains had failed to recapitulate this property. Here we report the engineering and characterization of phage display libraries of stable human VH domains, and the selection of binders against a diverse set of antigens. Unlike "camelized" human domains, the domains do not rely on potentially immunogenic framework mutations and maintain the structure of the VH/VL interface. Structure determination in complex with hen egg-white lysozyme revealed an extended VH binding interface, with complementarity determining region 3 (CDR3) deeply penetrating into the active site cleft, highly reminiscent to what has been observed for camelid domains. Taken together, our results demonstrate that fully human VH domains can be constructed that are not only stable and well-expressed, but also rival the cleft binding properties of camelid antibodies. Fully human VH single domains that rival the stability and cleft recognition of camelid antibodies.,Rouet R, Dudgeon K, Christie M, Langley D, Christ D J Biol Chem. 2015 Mar 3. pii: jbc.M114.614842. PMID:25737448[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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