9vx3
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the peptide-bound form of HisMab-1 Fv-clasp== | |
| + | <StructureSection load='9vx3' size='340' side='right'caption='[[9vx3]], [[Resolution|resolution]] 2.39Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9vx3]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VX3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VX3 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]] 2.39Å</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=9vx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vx3 OCA], [https://pdbe.org/9vx3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vx3 RCSB], [https://www.ebi.ac.uk/pdbsum/9vx3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vx3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/STK4_HUMAN STK4_HUMAN] Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.<ref>PMID:8816758</ref> <ref>PMID:8702870</ref> <ref>PMID:11278283</ref> <ref>PMID:11517310</ref> <ref>PMID:12757711</ref> <ref>PMID:15109305</ref> <ref>PMID:16510573</ref> <ref>PMID:16751106</ref> <ref>PMID:16930133</ref> <ref>PMID:17932490</ref> <ref>PMID:18328708</ref> <ref>PMID:18986304</ref> <ref>PMID:19525978</ref> <ref>PMID:21245099</ref> <ref>PMID:21512132</ref> <ref>PMID:21212262</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The polyhistidine tag (His-tag) is one of the most widely used peptide tags for the purification of recombinant proteins, owing to its compatibility with immobilized metal affinity chromatography. While numerous anti-His-tag antibodies are commercially available, their quantitative affinity data and structural insights are limited. Here, we present a detailed physicochemical and structural characterization of a novel anti-His-tag antibody, HisMab-1. Isothermal titration calorimetry showed that the Fab fragment of HisMab-1 binds to a hexahistidine peptide in an enthalpy-driven manner, with a dissociation constant (K(D)) of approximately 30 nM at a neutral pH. The crystal structure of the HisMab-1-hexahistidine peptide complex at 2.39-A resolution revealed that HisMab-1 primarily recognizes the first, second, fourth, and fifth histidine residues of the peptide through multiple interactions, including hydrogen bonding and pi-pi stacking, which collectively contribute to the high specificity of the antibody. Notably, HisMab-1 also binds to a His-tag embedded within a conformationally constrained beta-hairpin loop without reducing affinity, highlighting its structural adaptability. These findings establish HisMab-1 as a high-affinity, high-specificity, structurally validated anti-His-tag antibody with broad potential in diverse protein engineering and structural biology applications. | ||
| - | + | Functional and Structural Characterization of a Novel Anti-His-tag Antibody, HisMab-1.,Hitomi N, Hoshi S, Kaneko MK, Kato R, Iwasaki K, Takagi J, Kato Y, Harada-Hikita A, Arimori T J Mol Biol. 2025 Dec 3;438(2):169574. doi: 10.1016/j.jmb.2025.169574. PMID:41349762<ref>PMID:41349762</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9vx3" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Arimori T]] | ||
| + | [[Category: Harada-Hikita A]] | ||
| + | [[Category: Hitomi N]] | ||
Current revision
Crystal structure of the peptide-bound form of HisMab-1 Fv-clasp
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