6XJP

Crystal Structure of KPT-185 bound to CRM1 (537-DLTVK-541 to GLCEQ)

Summary for 6XJP

• Entry DOI: 10.2210/pdb6xjp/pdb
• Descriptor: GTP-binding nuclear protein Ran, Ran-specific GTPase-activating protein 1, Exportin-1, ... (6 entities in total)
• Functional Keywords: nuclear export, crm1, xpo1, exportin-1, protein transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 159123.43

Authors

Baumhardt, J.M.,Chook, Y.M. (deposition date: 2020-06-24, release date: 2021-01-27, Last modification date: 2024-11-06)

Primary citation

Walker, J.S.,Hing, Z.A.,Harrington, B.,Baumhardt, J.,Ozer, H.G.,Lehman, A.,Giacopelli, B.,Beaver, L.,Williams, K.,Skinner, J.N.,Cempre, C.B.,Sun, Q.,Shacham, S.,Stromberg, B.R.,Summers, M.K.,Abruzzo, L.V.,Rassenti, L.,Kipps, T.J.,Parikh, S.,Kay, N.E.,Rogers, K.A.,Woyach, J.A.,Coppola, V.,Chook, Y.M.,Oakes, C.,Byrd, J.C.,Lapalombella, R.
Recurrent XPO1 mutations alter pathogenesis of chronic lymphocytic leukemia.
J Hematol Oncol, 14:17-17, 2021

PubMed Abstract: Exportin 1 (XPO1/CRM1) is a key mediator of nuclear export with relevance to multiple cancers, including chronic lymphocytic leukemia (CLL). Whole exome sequencing has identified hot-spot somatic XPO1 point mutations which we found to disrupt highly conserved biophysical interactions in the NES-binding groove, conferring novel cargo-binding abilities and forcing cellular mis-localization of critical regulators. However, the pathogenic role played by change-in-function XPO1 mutations in CLL is not fully understood.

PubMed: 33451349
DOI: 10.1186/s13045-021-01032-2

Experimental method

X-RAY DIFFRACTION (2.802 Å)