Structural determinants of nuclear export signal orientation in binding to exportin CRM1.
The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). Comparison of minus and plus NESs identified structural and sequence determinants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome.
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States.
Ho Yee Joyce
http://orcid.org/0000-0002-0502-1957
HY
Fung
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States.
Szu-Chin
SC
Fu
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States.
Chad A
CA
Brautigam
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States.
Yuh Min
YM
Chook
D018360:Crystallography, X-Ray; D006801:Humans; D028884:Karyopherins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D049790:Nuclear Export Signals; D011485:Protein Binding; D011487:Protein Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism*; D000097606:Exportin 1 Protein
D028884:Karyopherins; D049790:Nuclear Export Signals; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein
CRM1; S. cerevisiae; biochemistry; biophysics; exportin-1; human; nuclear export signal; nuclear transport; structural biology; viruses