Design, production and characterization of FLIN2 and FLIN4: the engineering of intramolecular ldb1 : LMO complexes
Details
Publication Year 2001-07,Volume 14,Issue #7,Page 493-499
Journal Title
PROTEIN ENGINEERING
Publication Type
Journal Article
Abstract
The nuclear LIM-only (LMO) transcription factors LMO2 and LMO4 play important roles in both normal and leukemic T-cell development. LIM domains are cysteine/ histidine-rich domains that contain two structural zinc ions and that function as protein-protein adaptors; members of the LMO family each contain two closely spaced LIM domains. These LMO proteins all bind with high affinity to the nuclear protein LIM domain binding protein 1 (ldb1). The LMO-ldb1 interaction is mediated through the N-terminal LIM domain (LIM1) of LMO proteins and a 38-residue region towards the C-terminus of ldb1 [ldb1(LID)]. Unfortunately, recombinant forms of LMO2 and LMO4 have limited solubility and stability, effectively preventing structural analysis. Therefore, we have designed and constructed a fusion protein in which Idb1(LID) and LIM1 of LMO2 can form an intramolecular complex. The engineered protein, FLIN2 (fusion of the LIM interacting domain of ldb1 and the N-terminal LIM domain of LMO2) has been expressed and purified in milligram quantities. FLIN2 is monomeric, contains significant levels of secondary structure and yields a sharp and well-dispersed one-dimensional H-1 NMR spectrum. The analogous LMO4 protein, FLIN4, has almost identical properties. These data suggest that we will be able to obtain high-resolution structural information about the LMO-ldb1 interactions.
Publisher
OXFORD UNIV PRESS
Keywords
CYSTEINE-RICH PROTEIN; TERMINAL LIM DOMAIN; HOMEODOMAIN PROTEINS; CIRCULAR-DICHROISM; INTERACTOR NLI; CRP2; LMO2; DIFFERENTIATION; TRANSLOCATIONS; IDENTIFICATION
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Creation Date: 2001-07-01 12:00:00
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