1m1l
From Proteopedia
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Human Suppressor of Fused (N-terminal domain)
Contents |
Overview
The Hedgehog pathway drives proliferation and differentiation by, activating the Gli/Ci family of zinc finger transcription factors. Gli/Ci, proteins form Hedgehog signaling complexes with other signaling, components, including the kinesin-like protein Costal-2, the, serine-threonine kinase Fused, and Suppressor of Fused [Su(fu)]. In these, complexes Gli/Ci proteins are regulated by cytoplasmic sequestration, phosphorylation, and proteolysis. Here we characterize structural and, functional determinants of Su(fu) required for Gli regulation and show, that Su(fu) contains at least two distinct domains: a highly conserved, carboxy-terminal region required for binding to the amino-terminal ends of, the Gli proteins and a unique amino-terminal domain that binds the, carboxy-terminal tail of Gli1. While each domain is capable of binding to, different Gli1 regions independently, interactions between Su(fu) and Gli1, at both sites are required for cytoplasmic tethering and repression of, Gli1. Furthermore, we have solved the crystal structure of the, amino-terminal domain of human Su(fu)(27-268) at 2.65 A resolution. This, domain forms a concave pocket with a prominent acidic patch. Mutation at, Asp(159) in the acidic patch disrupts Gli1 tethering and repression while, not strongly disrupting binding, indicating that the amino-terminal domain, of Su(fu) likely impacts Gli binding through a mechanism distinct from, that for tethering and repression. These studies provide a structural, basis for understanding the function of Su(fu).
Disease
Known disease associated with this structure: Medulloblastoma, desmoplastic OMIM:[607035]
About this Structure
1M1L is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Suppressor of fused regulates Gli activity through a dual binding mechanism., Merchant M, Vajdos FF, Ultsch M, Maun HR, Wendt U, Cannon J, Desmarais W, Lazarus RA, de Vos AM, de Sauvage FJ, Mol Cell Biol. 2004 Oct;24(19):8627-41. PMID:15367681
Page seeded by OCA on Mon Nov 12 18:06:21 2007
