Platelet microbicidal protein 1: structural themes of a multifunctional antimicrobial peptide.
Mammalian platelets release platelet microbicidal proteins (PMPs) as components of their antimicrobial armamentarium. The present studies defined the structure of PMP-1 and examined its structure-activity relationships. Amino acid sequencing and mass spectroscopy demonstrated that distinct N-terminal polymorphism variants of PMP-1 isolated from nonstimulated or thrombin-stimulated platelets arise from a single PMP-1 propeptide. Sequence data (NH(2)-[S]D(1)DPKE(5)SEGDL(10)HCVCV(15)KTTSL(20) . . .) enabled cloning of PMP-1 from bone marrow and characterization of its full-length cDNA. PMP-1 is translated as a 106-amino-acid precursor and is processed to yield 73-residue (8,053 Da) and 72-residue (7,951-Da) variants. Searches with the BLAST program and sequence alignments demonstrated the homology of PMP-1 to members of the mammalian platelet factor 4 (PF-4) family of proteins. On the basis of phylogenetic relatedness, congruent sequence motifs, and predicted three-dimensional structures, PMP-1 shares the greatest homology with human PF-4 (hPF-4). By integration of its structural and antimicrobial properties, these results establish the identity of PMP-1 as a novel rabbit analogue of the microbicidal chemokine (kinocidin) hPF-4. These findings advance the hypothesis that stimuli in the setting of infection prompt platelets to release PF-4-class or related kinocidins, which have structures consistent with their likely multiple roles that bridge molecular and cellular mechanisms of antimicrobial host defense.
Yount
Nannette Y
NY
David Geffen School of Medicine at UCLA, Division of Infectious Diseases, St. John's Cardiovascular Research Center, Research & Education Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Gank
Kimberly D
KD
Xiong
Yan Qiong
YQ
Bayer
Arnold S
AS
Pender
Thomas
T
Welch
William H
WH
Yeaman
Michael R
MR
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001185:Artificial Intelligence; D001798:Blood Proteins / Q000737:chemistry* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004563:Electrochemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D066298:In Vitro Techniques; D051741:Kruppel-Like Transcription Factors; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011817:Rabbits; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013917:Thrombin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D018076:DNA, Complementary; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; C115768:ZNF85 protein, human; C077150:platelet microbicidal protein, Oryctolagus cuniculus; D013917:Thrombin