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Characterizing the heterodimerization interface of core-binding factors (CBFs).

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Call No.	QP552.T68 Z53 2003
Author	Zhang, Lina, 1974-
Title	Characterizing the heterodimerization interface of core-binding factors (CBFs).
Date	2003
Abstract	Core-binding factors (CBFs) are a small family of transcription factors that play important roles in several developmental processes and in human disease. CBFs consist of CBFα (Runx1, Runx2, or Runx3) and CBFβ. The CBFα subunit binds DNA in a sequence-specific manner. The CBFβ subunit does not contact DNA directly but heterodimerizes with CBFα and increases its affinity for DNA. Both DNA binding and heterodimerization with CBFβ are mediated by a single domain in the CBFα subunits known as the 'Runt domain'. This thesis examined the Runt domain-CBFβ interface and determined the structural and functional contribution of the residues in the Runt domain to heterodimerization with CBFβ. Two residues, N109 and T161 were found to make the most significant energetic contribution to heterodimerization both in vitro and in vivo. The results refine the structural analyses and further our understanding of the Runx1-CBFβ interface. CBFβ-SMMHC, caused by inv ( 16 ) in leukemia cells, binds to the Runt domain with at least 10 fold higher affinity than CBFβ. A specific region in SMMHC contacts the Runt domain and contributes to this high affinity binding. We performed alanine mutagenesis to map the Runt domain binding site in the SMMHC portion of the CBFβ-SMMHC fusion protein.
Description	xiii, 163 leaves : ill. (some col.) 28 cm.
Format	application/pdf
Advisor	Nancy A. Speck.
Subject	Transcription factors. DNA-protein interactions. Genetic transcription -- Regulation.
College	Dartmouth Medical School -- Department of Biochemistry.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.16

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	Carol Folt Characterizing the Heterodimerization Interface of Core-Binding Factors (CBFs) A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the or ==== degree of Doctor of Philosophy III The Department of Biochemistry by LINAZHANG DARTMOUTH COLLEGE Hanover, New Hampshire May, 2003 Examining Co~tteel ~ , Ta Yuan Chang d[a~~nce C.Myers ' • ,... ) Dean of Graduate Studies )i

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Characterizing the heterodimerization interface of core-binding factors (CBFs).

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