The structure of the N-terminal domain of the product of the lissencephaly gene Lis1 and its functional implications - PubMed (original) (raw)

The structure of the N-terminal domain of the product of the lissencephaly gene Lis1 and its functional implications

Myung Hee Kim et al. Structure. 2004 Jun.

Free article

Abstract

Mutations in the Lis1 gene result in lissencephaly (smooth brain), a debilitating developmental syndrome caused by the impaired ability of postmitotic neurons to migrate to their correct destination in the cerebral cortex. Sequence similarities suggest that the LIS1 protein contains a C-terminal seven-blade beta-propeller domain, while the structure of the N-terminal fragment includes the LisH (Lis-homology) motif, a pattern found in over 100 eukaryotic proteins with a hitherto unknown function. We present the 1.75 A resolution crystal structure of the N-terminal domain of mouse LIS1, and we show that the LisH motif is a novel, thermodynamically very stable dimerization domain. The structure explains the molecular basis of a low severity form of lissencephaly.

PubMed Disclaimer

Publication types

MeSH terms

Substances

LinkOut - more resources