| Structural highlights
Function
PLXB1_HUMAN Receptor for SEMA4D. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Signaling by single-pass transmembrane receptors often involves a formation of ligand-induced receptor dimers with particular conformation, and bivalent receptor binders can modulate receptor functions by inducing different receptor dimer conformations, although such agents are difficult to design. Here, we describe the generation of both antagonistic and agonistic receptor dimerizers toward PlexinB1 (PlxnB1), a receptor for semaphorin 4D (Sema4D), by grafting two different PlxnB1-binding peptides onto the human immunoglobulin G1 (IgG1) Fc protein. The function-modulating activity of a peptide Fc was strongly dependent on the type of the peptide as well as the grafting site, with the best variants showing activity at an nM concentration range. Structural analysis of each peptide-PlxnB1 complex revealed that the agonistic Fc dimerizes PlxnB1 in a face-to-face fashion similar to that induced by Sema4D, whereas antagonistic Fc would induce signaling-incompetent PlxnB1 dimer conformation, enforcing the idea that plexin activation is primarily controlled by the receptor orientation within the dimer.
De novo Fc-based receptor dimerizers differentially modulate PlexinB1 function.,Sugano-Nakamura N, Matoba K, Hirose M, Bashiruddin NK, Matsunaga Y, Yamashita K, Hirata K, Yamamoto M, Arimori T, Suga H, Takagi J Structure. 2022 Aug 10. pii: S0969-2126(22)00277-5. doi:, 10.1016/j.str.2022.07.008. PMID:35981535[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Giordano S, Corso S, Conrotto P, Artigiani S, Gilestro G, Barberis D, Tamagnone L, Comoglio PM. The semaphorin 4D receptor controls invasive growth by coupling with Met. Nat Cell Biol. 2002 Sep;4(9):720-4. PMID:12198496 doi:10.1038/ncb843
- ↑ Aurandt J, Vikis HG, Gutkind JS, Ahn N, Guan KL. The semaphorin receptor plexin-B1 signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12085-90. Epub 2002 Aug 26. PMID:12196628 doi:10.1073/pnas.142433199
- ↑ Swiercz JM, Kuner R, Offermanns S. Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2. J Cell Biol. 2004 Jun 21;165(6):869-80. PMID:15210733 doi:10.1083/jcb.200312094
- ↑ Tong Y, Hota PK, Penachioni JY, Hamaneh MB, Kim S, Alviani RS, Shen L, He H, Tempel W, Tamagnone L, Park HW, Buck M. Structure and function of the intracellular region of the plexin-b1 transmembrane receptor. J Biol Chem. 2009 Dec 18;284(51):35962-72. Epub . PMID:19843518 doi:10.1074/jbc.M109.056275
- ↑ Janssen BJ, Robinson RA, Perez-Branguli F, Bell CH, Mitchell KJ, Siebold C, Jones EY. Structural basis of semaphorin-plexin signalling. Nature. 2010 Sep 26. PMID:20877282 doi:10.1038/nature09468
- ↑ Bell CH, Aricescu AR, Jones EY, Siebold C. A Dual Binding Mode for RhoGTPases in Plexin Signalling. PLoS Biol. 2011 Aug;9(8):e1001134. Epub 2011 Aug 30. PMID:21912513 doi:10.1371/journal.pbio.1001134
- ↑ Sugano-Nakamura N, Matoba K, Hirose M, Bashiruddin NK, Matsunaga Y, Yamashita K, Hirata K, Yamamoto M, Arimori T, Suga H, Takagi J. De novo Fc-based receptor dimerizers differentially modulate PlexinB1 function. Structure. 2022 Aug 10. pii: S0969-2126(22)00277-5. doi:, 10.1016/j.str.2022.07.008. PMID:35981535 doi:http://dx.doi.org/10.1016/j.str.2022.07.008
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