6lz4

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Crystal structure of PMab-1 Fv-clasp fragment with its antigen peptideCrystal structure of PMab-1 Fv-clasp fragment with its antigen peptide

Structural highlights

6lz4 is a 6 chain structure with sequence from Mus musculus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.49Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PDPN_MOUSE Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activation in platelets and leading to platelet activation and/or aggregation (PubMed:14522983, PubMed:15231832, PubMed:20110424, PubMed:17616532). Interaction with CD9, on the contrary, attenuates platelet aggregation and pulmonary metastasis induced by PDPN. Mediates effects on cell migration and adhesion through its different partners. Through MSN or EZR interaction promotes epithelial-mesenchymal transition (EMT) leading to ERZ phosphorylation and triggering RHOA activation leading to cell migration increase and invasiveness. Interaction with CD44 promotes directional cell migration in epithelial and tumor cells (By similarity). In lymph nodes (LNs), controls fibroblastic reticular cells (FRCs) adhesion to the extracellular matrix (ECM) and contraction of the actomyosin by maintaining ERM proteins (EZR; MSN and RDX) and MYL9 activation through association with unknown transmembrane proteins. Engagement of CLEC1B by PDPN promotes FRCs relaxation by blocking lateral membrane interactions leading to reduction of ERM proteins (EZR; MSN and RDX) and MYL9 activation (PubMed:25347465). Through binding with LGALS8 may participate in connection of the lymphatic endothelium to the surrounding extracellular matrix (By similarity). In keratinocytes, induces changes in cell morphology showing an elongated shape, numerous membrane protrusions, major reorganization of the actin cytoskeleton, increased motility and decreased cell adhesion (PubMed:10574709). Controls invadopodia stability and maturation leading to efficient degradation of the extracellular matrix (ECM) in tumor cells through modulation of RHOC activity in order to activate ROCK1/ROCK2 and LIMK1/LIMK2 and inactivation of CFL1 (By similarity). Required for normal lung cell proliferation and alveolus formation at birth (PubMed:12654292). Does not function as a water channel or as a regulator of aquaporin-type water channels (By similarity). Does not have any effect on folic acid or amino acid transport (PubMed:12032185).[UniProtKB:Q86YL7][1] [2] [3] [4] [5] [6] [7] [8]

Publication Abstract from PubMed

The MAP tag system comprises a 14-residue peptide derived from mouse podoplanin and its high-affinity monoclonal antibody PMab-1. We determined the crystal structure of PMab-1 complexed with the MAP tag peptide and found that the recognition required only the N-terminal 8-residues of MAP tag sequence, enabling the shortening of the tag length without losing the affinity for PMab-1. Furthermore, the structure illustrated that the MAP tag adopts a U-shaped conformation when bound by PMab-1, suggesting that loop-inserted MAP tag would assume conformation compatible with the PMab-1 binding. We inserted the 8-residue MAP tag into multiple loop regions in various proteins including fibronectin type III domain and G protein-coupled receptors and tested if they maintain PMab-1 reactivity. Despite the conformational restraints forced by the insertion position, all MAP-inserted mutants were expressed well in mammalian cells at levels comparable to the non-tagged proteins. Furthermore, the binding by PMab-1 was fully maintained even for the mutant where MAP tag was inserted at a structurally restricted beta-hairpin, indicating that the MAP tag system has unique feature that allows placement in the middle of protein domain at desired locations. Our results indicate the versatile utility of the MAP tag system in "site-specific epitope insertion" application.

Site-specific epitope insertion into recombinant proteins using the MAP tag system.,Wakasa A, Kaneko MK, Kato Y, Takagi J, Arimori T J Biochem. 2020 May 9. pii: 5835287. doi: 10.1093/jb/mvaa054. PMID:32386302[9]

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

See Also

References

  1. ↑ Scholl FG, Gamallo C, Vilaró S, Quintanilla M. Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes. J Cell Sci. 1999 Dec;112 ( Pt 24):4601-13. PMID:10574709 doi:10.1242/jcs.112.24.4601
  2. ↑ Boucherot A, Schreiber R, Pavenstädt H, Kunzelmann K. Cloning and expression of the mouse glomerular podoplanin homologue gp38P. Nephrol Dial Transplant. 2002 Jun;17(6):978-84. PMID:12032185 doi:10.1093/ndt/17.6.978
  3. ↑ Ramirez MI, Millien G, Hinds A, Cao Y, Seldin DC, Williams MC. T1alpha, a lung type I cell differentiation gene, is required for normal lung cell proliferation and alveolus formation at birth. Dev Biol. 2003 Apr 1;256(1):61-72. PMID:12654292 doi:10.1016/s0012-1606(02)00098-2
  4. ↑ Kato Y, Fujita N, Kunita A, Sato S, Kaneko M, Osawa M, Tsuruo T. Molecular identification of Aggrus/T1alpha as a platelet aggregation-inducing factor expressed in colorectal tumors. J Biol Chem. 2003 Dec 19;278(51):51599-605. PMID:14522983 doi:10.1074/jbc.M309935200
  5. ↑ Kaneko M, Kato Y, Kunita A, Fujita N, Tsuruo T, Osawa M. Functional sialylated O-glycan to platelet aggregation on Aggrus (T1alpha/Podoplanin) molecules expressed in Chinese hamster ovary cells. J Biol Chem. 2004 Sep 10;279(37):38838-43. PMID:15231832 doi:10.1074/jbc.M407210200
  6. ↑ Suzuki-Inoue K, Kato Y, Inoue O, Kaneko MK, Mishima K, Yatomi Y, Yamazaki Y, Narimatsu H, Ozaki Y. Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated platelet activation, by cancer cells. J Biol Chem. 2007 Sep 7;282(36):25993-6001. PMID:17616532 doi:10.1074/jbc.M702327200
  7. ↑ Uhrin P, Zaujec J, Breuss JM, Olcaydu D, Chrenek P, Stockinger H, Fuertbauer E, Moser M, Haiko P, Fässler R, Alitalo K, Binder BR, Kerjaschki D. Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation. Blood. 2010 May 13;115(19):3997-4005. PMID:20110424 doi:10.1182/blood-2009-04-216069
  8. ↑ Astarita JL, Cremasco V, Fu J, Darnell MC, Peck JR, Nieves-Bonilla JM, Song K, Kondo Y, Woodruff MC, Gogineni A, Onder L, Ludewig B, Weimer RM, Carroll MC, Mooney DJ, Xia L, Turley SJ. The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture. Nat Immunol. 2015 Jan;16(1):75-84. PMID:25347465 doi:10.1038/ni.3035
  9. ↑ Wakasa A, Kaneko MK, Kato Y, Takagi J, Arimori T. Site-specific epitope insertion into recombinant proteins using the MAP tag system. J Biochem. 2020 May 9. pii: 5835287. doi: 10.1093/jb/mvaa054. PMID:32386302 doi:http://dx.doi.org/10.1093/jb/mvaa054

6lz4, resolution 2.49Å

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