Dimerization and heme binding are conserved in amphibian and starfish homologues of the microRNA processing protein DGCR8.

Authors

Rachel Senturia, University of California Los AngelesFollow
Arthur Laganowsky, University of California Los Angeles
Ian Barr, University of California Los AngelesFollow
Brooke D. Scheidemantle, University of California Los AngelesFollow
Feng Guo, University of California Los AngelesFollow

Department

Natural Sciences and Mathematics

Document Type

Article

Source

PLoS One

Publication Date

1-1-2012

ISSN

1932-6203

Volume

7

Issue

7

First Page

39688

Last Page

39688

Abstract

Human DiGeorge Critical Region 8 (DGCR8) is an essential microRNA (miRNA) processing factor that is activated via direct interaction with Fe(III) heme. In order for DGCR8 to bind heme, it must dimerize using a dimerization domain embedded within its heme-binding domain (HBD). We previously reported a crystal structure of the dimerization domain from human DGCR8, which demonstrated how dimerization results in the formation of a surface important for association with heme. Here, in an attempt to crystallize the HBD, we search for DGCR8 homologues and show that DGCR8 from Patiria miniata (bat star) also binds heme. The extinction coefficients (ε) of DGCR8-heme complexes are determined; these values are useful for biochemical analyses and allow us to estimate the heme occupancy of DGCR8 proteins. Additionally, we present the crystal structure of the Xenopus laevis dimerization domain. The structure is very similar to that of human DGCR8. Our results indicate that dimerization and heme binding are evolutionarily conserved properties of DGCR8 homologues not only in vertebrates, but also in at least some invertebrates.

PubMed ID

22768307

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.