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Integrative Threading of the DNA-PKcs Disordered Region with Crosslinking Restraints

ABSTRACT: Integrative structure modelling was applied to understand how auto-phosphorylation of the ABCDE cluster in DNA-PKcs can occur. We used crosslinking restraints to assign sequence to structurally unassigned helices in DNA-PKcs s in the largely disordered region containing the ABCDE cluster. Our final model positions the ABCDE cluster at the end of the second helices, suggesting that phosphorylation occurs through trans-auto-phosphorylation, or through a large conformational change in the disordered region for cis-auto-phosphorylation.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Morgan Hepburn

LAB HEAD: David C. Schriemer

PROVIDER: PXD016639 | Pride | 2019-12-10

REPOSITORIES: Pride

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SSEThread: Integrative threading of the DNA-PKcs sequence based on data from chemical cross-linking and hydrogen deuterium exchange.

Saltzberg Daniel J DJ Hepburn Morgan M Pilla Kala Bharath KB Schriemer David C DC Lees-Miller Susan P SP Blundell Tom L TL Sali Andrej A

Progress in biophysics and molecular biology 20190927

X-ray crystallography and electron microscopy maps resolved to 3-8 Å are generally sufficient for tracing the path of the polypeptide chain in space, while often insufficient for unambiguously registering the sequence on the path (i.e., threading). Frequently, however, additional information is available from other biophysical experiments, physical principles, statistical analyses, and other prior models. Here, we formulate an integrative approach for sequence assignment to a partial backbone mo ...[more]

PMID: 31570166

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