Crystallization of cytoplasmic actin in complex with deoxyribonuclease I

Mannherz, Hans Georg; Kabsch, Wolfgang; Suck, Dietrich; Friebel, Klaus; Frimmer, M.

doi:10.1042/bj2250517

Cited by 8 publications

(2 citation statements)

References 22 publications

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“…The root-meansquare error is 0.7 A. Comparison of cytoplasmic and skeletal muscle actin structure Crystals of a cytoplasmic (porcine liver) actin in complex with DNase I were also obtained (Mannherz et al, 1985). These crystals were found to be isomorphous to the orthorhombic type III crystals containing rabbit skeletal muscle actin although the two actins differ in 25 amino acids.…”

Section: Resultsmentioning

confidence: 99%

Three-dimensional structure of the complex of actin and DNase I at 4.5 A resolution.

Kabsch¹,

Mannherz²,

Suck³

1985

The EMBO Journal

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The shape of an actin subunit has been derived from an improved 6 A map of the complex of rabbit skeletal muscle actin and bovine pancreatic DNase I obtained by X‐ray crystallographic methods. The three‐dimensional structure of DNase I determined independently at 2.5 A resolution was compared with the DNase I electron density in the actin:DNase map. The two structures are very similar at 6 A resolution thus leading to an unambiguous identification of actin as well as DNase I electron density. Furthermore the correct hand of the actin structure is determined from the DNase I atomic structure. The resolution of the actin structure was extended to 4.5 A by using a single heavy‐atom derivative and the knowledge of the atomic coordinates of DNase I. The dimensions of an actin subunit are 67 A X 40 A X 37 A. It consists of a small and a large domain, the small domain containing the N terminus. Actin is an alpha,beta‐protein with a beta‐pleated sheet in each domain. These sheets are surrounded by several alpha‐helices, comprising at least 40% of the structure. The phosphate peak of the adenine nucleotide is located between the two domains. The complex of actin and DNase I as found in solution (i.e., the actin:DNase I contacts which do not depend on crystal packing) was deduced from a comparison of monoclinic with orthorhombic crystals. Residues 44‐46, 51, 52, 60‐62 of DNase I are close to a loop region in the small domain of actin. At a distance of approximately 15 A there is a second contact in the large domain in which Glu13 of DNase I is involved. A possible binding region for myosin is discussed.

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Section: Resultsmentioning

confidence: 99%

Three-dimensional structure of the complex of actin and DNase I at 4.5 A resolution.

Kabsch¹,

Mannherz²,

Suck³

1985

The EMBO Journal

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“…Two alternative possibilities for the acceleration of the DNase I activity by C1q can therefore be hypothesized. Either, in analogy to SAP (23), C1q may increase the access of DNase to the DNA in the chromatin of necrotic cells by displacing the DNA binding proteins, or C1q may block the immobilization of DNase by components of the actin cytoskeleton (59)(60)(61) and, as a consequence, increase the access of DNase to the chromatin.…”

Section: Discussionmentioning

confidence: 99%

Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

Gaipl¹,

Beyer²,

Heyder³

et al. 2004

Arthritis & Rheumatism

105

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Objective. The efficient uptake of dying cells by phagocytes is essential to the avoidance of chronic inflammation. Some human autoimmune responses are thought to be driven by autoantigens from apoptotic or necrotic cells. We analyzed the role of C1q and DNase I in the disposal of necrotic cell-derived chromatin because deficiencies in these serum factors predispose to the development of systemic autoimmune disorders, such as systemic lupus erythematosus.Methods. Human necrotic peripheral blood lymphocytes were incubated in cell culture medium supplemented with various sera or serum components. Chromatin degradation was monitored by measuring the residual DNA content by flow cytometry. The uptake of necrotic cell-derived nuclei was analyzed by in vitro phagocytosis assays.Results. Reconstitution of C1q-depleted serum with C1q strongly increased its ability to degrade necrotic cell-derived chromatin. Although C1q itself displayed no DNase activity, it strongly augmented the activity of serum DNase I. Whereas an excess of recombinant DNase I degraded chromatin in the absence of C1q, efficient uptake of the predigested material by monocyte-derived phagocytes required the presence of C1q. These data show that C1q and DNase I cooperate in the degradation of chromatin from necrotic cells. Furthermore, C1q was found to be necessary for effective uptake of degraded chromatin by monocyte-derived phagocytes.Conclusion. C1q or DNase I deficiencies may precipitate autoimmunity in humans by a mechanism similar to that of other molecules that are involved in the safe, efficient, and rapid disposal of dying cells.

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Die Molekülstruktur des Aktins: Implikationen für Motilität und Kontraktilität

Mannherz

1992

Nachr. Chem. Tech. Lab.

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Crystallization of cytoplasmic actin in complex with deoxyribonuclease I

Cited by 8 publications

References 22 publications

Three-dimensional structure of the complex of actin and DNase I at 4.5 A resolution.

Three-dimensional structure of the complex of actin and DNase I at 4.5 A resolution.

Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

Die Molekülstruktur des Aktins: Implikationen für Motilität und Kontraktilität

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