Protein residue network analysis reveals fundamental properties of the human coagulation factor VIII

Autor(es)

Lopes, Tiago J. S. ^[1] ; Rios, Ricardo ^{[2, 3]} ; Nogueira, Tatiane ^{[2, 3]} ; Mello, Rodrigo F. ^{[2, 4]}

Afiliação do(s) autor(es)

^[1] Natl Ctr Child Hlth & Dev, Res Inst, Ctr Regenerat Med, Dept Reprod Biol, Setagaya Ku, 2-10-1 Okura, Tokyo 1578535 - Japan

^[2] Univ Sao Paulo, Inst Math & Comp Sci, Sao Paulo - Brazil

^[3] Univ Fed Bahia, Dept Comp Sci, Salvador, BA - Brazil

^[4] Itau Unibanco, Av Engn Armando Arruda Pereira 707, BR-04309010 Jabaquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 11, n. 1 JUN 16 2021.
• Citações Web of Science: 0

Resumo

Hemophilia A is an X-linked inherited blood coagulation disorder caused by the production and circulation of defective coagulation factor VIII protein. People living with this condition receive either prophylaxis or on-demand treatment, and approximately 30% of patients develop inhibitor antibodies, a serious complication that limits treatment options. Although previous studies performed targeted mutations to identify important residues of FVIII, a detailed understanding of the role of each amino acid and their neighboring residues is still lacking. Here, we addressed this issue by creating a residue interaction network (RIN) where the nodes are the FVIII residues, and two nodes are connected if their corresponding residues are in close proximity in the FVIII protein structure. We studied the characteristics of all residues in this network and found important properties related to disease severity, interaction to other proteins and structural stability. Importantly, we found that the RIN-derived properties were in close agreement with in vitro and clinical reports, corroborating the observation that the patterns derived from this detailed map of the FVIII protein architecture accurately capture the biological properties of FVIII. (AU)

• Processo FAPESP: 13/07375-0 - CeMEAI - Centro de Ciências Matemáticas Aplicadas à Indústria
• Beneficiário: Francisco Louzada Neto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs