8oi2
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Alb1 megabody in complex with human serum albumin== | |
| + | <StructureSection load='8oi2' size='340' side='right'caption='[[8oi2]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8oi2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_G27 Helicobacter pylori G27] 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=8OI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OI2 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</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=8oi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8oi2 OCA], [https://pdbe.org/8oi2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8oi2 RCSB], [https://www.ebi.ac.uk/pdbsum/8oi2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8oi2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:[https://omim.org/entry/103600 103600]. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.<ref>PMID:8048949</ref> <ref>PMID:7852505</ref> <ref>PMID:9329347</ref> <ref>PMID:9589637</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.<ref>PMID:19021548</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The pharmacokinetic properties of small biotherapeutics can be enhanced via conjugation to cross-reactive albumin-binding ligands in a process that improves their safety and accelerates testing through multiple pre-clinical animal models. In this context, the small and stable heavy-chain-only nanobody NbAlb1, capable of binding both human and murine albumin, has recently been successfully applied to improve the stability and prolong the in vivo plasma residence time of multiple small therapeutic candidates. Despite its clinical efficacy, the mechanism of cross-reactivity of NbAlb1 between human and murine serum albumins has not yet been investigated. To unveil the molecular basis of such an interaction, we solved the crystal structure of human serum albumin (hSA) in complex with NbAlb1. The structure was obtained by harnessing the unique features of a megabody chimeric protein, comprising NbAlb1 grafted onto a modified version of the circularly permutated and bacterial-derived protein HopQ. This structure showed that NbAlb1 contacts a yet unexplored binding site located in the peripheral region of domain II that is conserved in both human and mouse serum albumin proteins. Furthermore, we show that the binding of NbAlb1 to both serum albumin proteins is retained even at acidic pH levels, thus explaining its extended in vivo half-life. The elucidation of the molecular basis of NbAlb1 cross-reactivity to human and murine albumins might guide the design of novel nanobodies with broader reactivity toward a larger panel of serum albumins, thus facilitating the pre-clinical and clinical phases in humans. | ||
| - | + | Crystal structure of human serum albumin in complex with megabody reveals unique human and murine cross-reactive binding site.,De Felice S, Romanyuk Z, Chinellato M, Zoia G, Linciano S, Kumada Y, Pardon E, Steyaert J, Angelini A, Cendron L Protein Sci. 2024 Feb;33(2):e4887. doi: 10.1002/pro.4887. PMID:38152025<ref>PMID:38152025</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Angelini | + | <div class="pdbe-citations 8oi2" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Helicobacter pylori G27]] |
| - | [[Category: Zoia | + | [[Category: Homo sapiens]] |
| + | [[Category: Large Structures]] | ||
| + | [[Category: Angelini A]] | ||
| + | [[Category: Cendron L]] | ||
| + | [[Category: De Felice S]] | ||
| + | [[Category: Pardon E]] | ||
| + | [[Category: Romanyuk Z]] | ||
| + | [[Category: Steyaert J]] | ||
| + | [[Category: Zoia G]] | ||
Current revision
Crystal structure of Alb1 megabody in complex with human serum albumin
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