Solution Structure and Dynamics of Myeloid Progenitor Inhibitory Factor-1 (MPIF-1), A Novel Monomeric CC Chemokine

Krishna Rajarathnam, Yuling Li, Thomas Rohrer, Reiner Gentz

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

MPIF-1, a CC chemokine, is a specific inhibitor of myeloid progenitor cells and is the most potent activator of monocytes. The solution structure of myeloid progenitor inhibitor factor-1 (MPIF-1) has been determined by NMR spectroscopy. The structure reveals that MPIF-1 is a monomer with a well defined core except for termini residues and adopts the chemokine fold of three β-strands and an overlying α-helix. In addition to the four cysteines that characterize most chemokines, MPIF-1 has two additional cysteines that form a disulfide bond. The backbone dynamics indicate that the disulfide bonds and the adjacent residues that include the functionally important N-terminal and N-terminal loop residues show significant dynamics. MPIF-1 is a highly basic protein (pI >9), and the structure reveals distinct positively charged pockets that could be correlated to proteoglycan binding. MPIF-1 is processed from a longer proprotein at the N terminus and the latter is also functional though with reduced potency, and both proteins exist as monomers under a variety of solution conditions. MPIF-1 is therefore unique because longer proproteins of all other chemokines oligomerize in solution. The MPIF-1 structure should serve as a template for future functional studies that could lead to therapeutics for preventing chemotherapy-associated myelotoxicity.

Original languageEnglish (US)
Pages (from-to)4909-4916
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number7
DOIs
StatePublished - Feb 16 2001

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CC Chemokines
Chemokines
Disulfides
Cysteine
Monomers
Myeloid Progenitor Cells
Chemotherapy
Proteoglycans
Nuclear magnetic resonance spectroscopy
Monocytes
Proteins
Magnetic Resonance Spectroscopy
Drug Therapy
Therapeutics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Solution Structure and Dynamics of Myeloid Progenitor Inhibitory Factor-1 (MPIF-1), A Novel Monomeric CC Chemokine. / Rajarathnam, Krishna; Li, Yuling; Rohrer, Thomas; Gentz, Reiner.

In: Journal of Biological Chemistry, Vol. 276, No. 7, 16.02.2001, p. 4909-4916.

Research output: Contribution to journalArticle

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