Nghiên cứu tác động của các biến đổi sau dịch mã lên cấu trúc xương của protein

Amino Acids - Tập 51 - Trang 1065-1079 - 2019
Pierrick Craveur1,2,3,4,5, Tarun J. Narwani1,2,3,4, Joseph Rebehmed1,2,3,4,6, Alexandre G. de Brevern1,2,3,4
1INSERM UMR_S 1134, BIGR, DSIMB, Paris, France
2Université de Paris, Université de la Réunion, l’Université des Antilles, UMR_S 1134, Paris Cedex 15, France
3Institut National de la Transfusion Sanguine (INTS), Paris, France
4Laboratoire d'Excellence GR-Ex, Paris, France
5Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, USA
6Department of Computer Science and Mathematics, Lebanese American University, Byblos, Lebanon

Tóm tắt

Các biến đổi sau dịch mã (PTMs) được biết đến đóng vai trò quan trọng trong việc điều tiết chức năng của protein. Tác động của chúng lên cấu trúc protein và sự liên kết với các vùng rối loạn đã được phát hiện trong thập kỷ qua. Tuy nhiên, sự đa dạng cao về các loại PTM và các sơ đồ khác nhau của các biến đổi protein (nhiều PTM, các loại khác nhau, vào các thời điểm khác nhau, v.v.) làm cho việc so sánh trực tiếp giữa các chú thích PTM và dữ liệu cấu trúc protein trở nên khó khăn. Do đó, chúng tôi đã phân tích tác động của các biến đổi tại vị trí lên cấu trúc protein ở cấp độ cục bộ. Nhờ vào cơ sở dữ liệu cấu trúc được tạo dựng đặc biệt, được gọi là PTM-SD, một màn sàng lọc lớn các PTM đã được thực hiện và phân tích ở các mức độ hình dạng protein cục bộ bằng cách sử dụng các khối protein cấu trúc (PBs). Chúng tôi đã điều tra mối quan hệ giữa các PTM với hình dạng xương của các dư lượng đã được biến đổi, với môi trường cục bộ của chúng, và ở cấp độ cấu trúc protein hoàn chỉnh. Hai loại PTM chính (N-glycosylation và phosphoryl hóa) đã được nghiên cứu trong các tập dữ liệu không lặp lại, và sau đó bốn protein khác nhau đã được tập trung, bao gồm ba loại PTM: N-glycosylation trong renin endopeptidase và carboxylesterase gan, phosphoryl hóa trong kinase phụ thuộc cyclin 2 (CDK2), và methyl hóa trong actin. Chúng tôi nhận thấy rằng các PTM có thể ổn định hoặc không ổn định cấu trúc xương, ở quy mô cục bộ và toàn cầu, và rằng các tác động này phụ thuộc vào các loại PTM.

Từ khóa

#biến đổi sau dịch mã #PTM #cấu trúc protein #N-glycosylation #phosphoryl hóa #methyl hóa

Tài liệu tham khảo

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