NMR solution structure of the 32-kDa platelet factor 4 ELR-motif N-terminal chimera: a symmetric tetramer

Biochemistry
K H MayoT J Daly

Abstract

Native human platelet factor 4 (PF4) is a homotetrameric protein (70 residues/subunit) known for its anticoagulant heparin binding activity. 2D 15N--1H HSQC NMR experiments of native PF4 in solution show the presence of conformational heterogeneity consistent with the formation of asymmetric homo-tetramers as observed in the X-ray crystal structure of both human and bovine PF4. A chimeric mutant of PF4 (called PF4-M2) which substitutes the first 11 N-terminal residues for the first eight residues from homologous interleukin-8 forms symmetric homo-tetramers with essentially the same heparin binding activity as native PF4. The solution structure of PF4-M2 has been investigated by using two- and three-dimensional 1H- and 15N-NMR spectroscopy and NOE-restrained simulated annealing molecular dynamics. As with other members of the CXC chemokine family whose structures are known, the PF4-M2 subunit monomer consists of a mostly hydrophobic, triple-stranded antiparallel beta-sheet onto which is folded an amphipathic C-terminal helix and a less periodic N-terminal domain. Although N-terminal substitution with the less acidic interleukin-8 sequence most affects the quarternary structure relative to native PF4 at the AC and AD dimer interf...Continue Reading

Citations

Jul 1, 1996·Protein Science : a Publication of the Protein Society·K H MayoH Park
Feb 1, 1997·Protein Science : a Publication of the Protein Society·V A DaraganK H Mayo
Mar 3, 1999·The Biochemical Journal·H YoungK H Mayo
Feb 15, 2001·The Biochemical Journal·A W GriffioenK H Mayo
Dec 14, 1999·Protein Science : a Publication of the Protein Society·A C LiwangP J Liwang
Jan 25, 2002·Annual Review of Pharmacology and Toxicology·Elias J Fernandez, Elias Lolis
Mar 13, 2016·Autoimmunity Reviews·Zheng CaiDouglas B Cines
Jan 13, 2006·Journal of Molecular Biology·Jan PilchErkki Ruoslahti
Sep 24, 2015·Nature Communications·Zheng CaiMark I Greene
Apr 4, 2017·International Journal of Molecular Sciences·Aaron J BrownKrishna Rajarathnam
Oct 5, 2017·International Journal of Molecular Sciences·Michelle C Miller, Kevin H Mayo
Jun 21, 2005·The Journal of Biological Chemistry·Nargès El GolliVéronique Briquet-Laugier
Nov 9, 2006·The Journal of Biological Chemistry·Aymeric A AmelotBernard F Le Bonniec
Aug 30, 2003·The Journal of Biological Chemistry·Kevin H MayoArjan W Griffioen
Mar 5, 2010·The Journal of Biological Chemistry·Ariane L JansmaDaniel Nietlispach
Dec 1, 2019·Cellular Signalling·Khanh T P NguyenDidier Dréau
Nov 13, 2021·Cellular and Molecular Life Sciences : CMLS·Philipp von HundelshausenKevin H Mayo

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