1f0m

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spinqualitylabelsall models 1f0m, resolution 2.2Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

MONOMERIC STRUCTURE OF THE HUMAN EPHB2 SAM (STERILE ALPHA MOTIF) DOMAIN

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The sterile alpha motif (SAM) domain is a protein module found in many, diverse signaling proteins. SAM domains in some systems have been shown to, self-associate. Previous crystal structures of an EphA4-SAM domain dimer, (Stapleton, D., Balan, I., Pawson, T., and Sicheri, F. (1999) Nat. Struct., Biol. 6, 44-49) and a possible EphB2-SAM oligomer (Thanos, C. D., Goodwill, K. E., and Bowie, J. U. (1999) Science 283, 833-836) both, revealed large interfaces comprising an exchange of N-terminal peptide, arms. Within the arm, a conserved hydrophobic residue (Tyr-8 in the, EphB2-SAM structure or Phe-910 in the EphA4-SAM structure) is anchored, into a hydrophobic cleft on a neighboring molecule. Here we have solved a, new crystal form of the human EphB2-SAM domain that has the same overall, SAM domain fold yet has no substantial intermolecular contacts. In the new, structure, the N-terminal peptide arm of the EphB2-SAM domain protrudes, out from the core of the molecule, leaving both the arm (including Tyr-8), and the hydrophobic cleft solvent-exposed. To verify that Tyr-8 is, solvent-exposed in solution, we made a Tyr-8 to Ala-8 mutation and found, that the EphB2-SAM domain structure and stability were only slightly, altered. These results suggest that Tyr-8 is not part of the hydrophobic, core of the EphB2-SAM domain and is conserved for functional reasons., Cystallographic evidence suggests a possible role for the N-terminal arm, in oligomerization. In the absence of a direct demonstration of biological, relevance, however, the functional role of the N-terminal arm remains an, open question.

Disease

Known diseases associated with this structure: Prostate cancer, progression and metastasis of OMIM:[600997]

About this Structure

1F0M is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Monomeric structure of the human EphB2 sterile alpha motif domain., Thanos CD, Faham S, Goodwill KE, Cascio D, Phillips M, Bowie JU, J Biol Chem. 1999 Dec 24;274(52):37301-6. PMID:10601296

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