Abstract
There is as yet no high-resolution data regarding the structure and organization of keratin intermediate filaments, which are obligate heteropolymers providing vital mechanical support in epithelia. We report the crystal structure of interacting 2B regions from the central coiled-coil domains of keratins 5 and 14 (K5 and K14), expressed in progenitor keratinocytes of epidermis. The interface of the K5-K14 coiled-coil heterodimer has asymmetric salt bridges, hydrogen bonds and hydrophobic contacts, and its surface exhibits a notable charge polarization. A trans-dimer homotypic disulfide bond involving Cys367 in K14's stutter region occurs in the crystal and in skin keratinocytes, where it is concentrated in a keratin filament cage enveloping the nucleus. We show that K14-Cys367 impacts nuclear shape in cultured keratinocytes and that mouse epidermal keratinocytes lacking K14 show aberrations in nuclear structure, highlighting a new function for keratin filaments.
| Original language | English |
|---|---|
| Pages (from-to) | 707-715 |
| Number of pages | 9 |
| Journal | Nature Structural and Molecular Biology |
| Volume | 19 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2012 |
Bibliographical note
Funding Information:We thank members of the Coulombe and Leahy laboratories for guidance and support, M. Becker and N. Venugopalan for beamline assistance, and S. Bailey for comments. General Medicine and Cancer Institutes Collaborative Access Team receives support from the US National Cancer Institute (Y1-CO-1020) and the National Institute of General Medical Sciences (Y1-GM-1104). Use of the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract DE-AC02-06CH11357. These studies were otherwise supported by US National Institutes of Health grants AR42047 (to P.A.C.) and HD055545 (to D.J.L.).