Histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and alters HagB-induced chemokine responses.
Histatins are human salivary gland peptides with anti-microbial and anti-inflammatory activities. In this study, we hypothesized that histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and attenuates HagB-induced chemokine responses in human myeloid dendritic cells. Histatin 5 bound to immobilized HagB in a surface plasmon resonance (SPR) spectroscopy-based biosensor system. SPR spectroscopy kinetic and equilibrium analyses, protein microarray studies, and I-TASSER structural modeling studies all demonstrated two histatin 5 binding sites on HagB. One site had a stronger affinity with a KD1 of 1.9 μM and one site had a weaker affinity with a KD2 of 60.0 μM. Binding has biological implications and predictive modeling studies and exposure of dendritic cells both demonstrated that 20.0 μM histatin 5 attenuated (p < 0.05) 0.02 μM HagB-induced CCL3/MIP-1α, CCL4/MIP-1β, and TNFα responses. Thus histatin 5 is capable of attenuating chemokine responses, which may help control oral inflammation.
Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
Derek S
DS
Borgwardt
SensíQ Technologies Inc., 800 Research Parkway, Suite 100, Oklahoma City, OK 73104, USA.
Aaron D
AD
Martin
Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
Jonathan R
JR
Van Hemert
Department of Computational Medicine & Bioinformatics, The University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109-2218, USA.
Jianyi
J
Yang
Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
Carol L
CL
Fischer
Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
Erica N
EN
Recker
Cellworks Research India Ltd, Whitefield, Bangalore, India.
Prashant R
PR
Nair
Cellworks Research India Ltd, Whitefield, Bangalore, India.
Robinson
R
Vidva
Cellworks Research India Ltd, Whitefield, Bangalore, India.
Shwetha
S
Chandrashekaraiah
Center for Molecular Microbiology and Department of Oral Biology, Box 100424, 1395 Center Drive, University of Florida, Gainesville, FL 32610, USA.
Ann
A
Progulske-Fox
1] Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA [2] Department of Endodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
David
D
Drake
Department of Biostatistics, College of Public Health, The University of Iowa, Iowa City, IA 52242, USA.
Joseph E
JE
Cavanaugh
Cellworks Group Inc., 2025 Gateway Place, San Jose, CA 95110, USA.
Shireen
S
Vali
Department of Computational Medicine & Bioinformatics, The University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109-2218, USA.
Yang
Y
Zhang
1] Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA [2] Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
Kim A
KA
Brogden
D018829:Adhesins, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D018925:Chemokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D054808:Histatins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D037102:Lectins / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology*
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D018925:Chemokines; C068075:HTN3 protein, human; C098582:HagB protein, Porphyromonas gingivalis; D054808:Histatins; D037102:Lectins