title: Structure and function of ameloblastin as an extracellular matrix protein: adhesion, calcium binding, and CD63 interaction in human and mouse.
abstract: The functional significance of extracellular matrix proteins in the life of vertebrates is underscored by a high level of sequence variability in tandem with a substantial degree of conservation in terms of cell-cell and cell-matrix adhesion interactions. Many extracellular matrix proteins feature multiple adhesion domains for successful attachment to substrates, such as integrin, CD63, and heparin. Here we have used homology and ab initio modeling algorithms to compare mouse ameloblastin (mAMBN) and human ameloblastin (hABMN) isoforms and to analyze their potential for cell adhesion and interaction with other matrix molecules as well as calcium binding. Sequence comparison between mAMBN and hAMBN revealed a 26-amino-acid deletion in mAMBN, corresponding to a helix-loop-helix frameshift. The human AMBN domain (174Q-201G), homologous to the mAMBN 157E-178I helix-loop-helix region, formed a helix-loop motif with an extended loop, suggesting a higher degree of flexibility of hAMBN compared with mAMBN, as confirmed by molecular dynamics simulation. Heparin-binding domains, CD63-interaction domains, and calcium-binding sites in both hAMBN and mAMBN support the concept of AMBN as an extracellular matrix protein. The high level of conservation between AMBN functional domains related to adhesion and differentiation was remarkable when compared with only 61% amino acid sequence homology.
authors.affiliation: Brodie Laboratory for Craniofacial Genetics, University of Illinois - Chicago, Chicago, IL 60612, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Thomas G H
authors.initials: TG
authors.lastname: Diekwisch
authors.forename: Xianghong
authors.initials: X
authors.lastname: Luan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D021982:Cell-Matrix Junctions; D002478:Cells, Cultured; D017124:Conserved Sequence; D003746:Dental Enamel Proteins / Q000737:chemistry* / Q000502:physiology*; D019143:Evolution, Molecular; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000502:physiology; D018257:Helix-Loop-Helix Motifs; D006493:Heparin / Q000378:metabolism; D006801:Humans; D051379:Mice; D056004:Molecular Dynamics Simulation; D010513:Periodontal Ligament / Q000166:cytology; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D060149:Tetraspanin 30 / Q000378:metabolism
chemical_list: C490889:AMBN protein, human; C490890:Ambn protein, mouse; D003746:Dental Enamel Proteins; D016326:Extracellular Matrix Proteins; D020033:Protein Isoforms; D060149:Tetraspanin 30; D006493:Heparin; D002118:Calcium