Biomedical subjects

Ziming Zhang

Publications and source records attributed to Ziming Zhang.

5 recordsLinked to original sources

PubMed2005

Small ubiquitin-like modifier (SUMO) recognition of a SUMO binding motif: a reversal of the bound orientation.

Sumoylation has recently been identified as an important mechanism that regulates protein interactions and localization in essential cellular functions, such as gene transcription, subnuclear structure formation, viral infection, and cell cycle progression. A SUMO binding amino acid sequence motif (SBM), which recognizes the SUMO moiety of modified proteins in sumoylation-dependent cellular functions, has been consistently identified by several recent studies. To understand the mechanism of SUMO recognition by the SBM, we have solved the solution structure of SUMO-1 in complex with a peptide containing the SBM derived from the protein PIASX (KVDVIDLTIESSSDEEEDPPAKR). Surprisingly, the structure reveals that the bound orientation of the SBM can reverse depending on the sequence context. The structure also reveals a novel mechanism of recognizing target sequences by a ubiquitin-like module. Unlike ubiquitin binding motifs, which all form helices and bind to the main beta-sheet of ubiquitin, the SBM forms an extended structure that binds between the alpha-helix and a beta-strand of SUMO-1. This study provides a clear mechanism of the SBM sequence variations and its recognition of the SUMO moiety in sumoylated proteins.

Amino Acid Motifs↗

PubMed2004

Structure and DNA-binding sites of the SWI1 AT-rich interaction domain (ARID) suggest determinants for sequence-specific DNA recognition.

ARID (AT-rich interaction domain) is a homologous family of DNA-binding domains that occur in DNA-binding proteins from a wide variety of species, ranging from yeast to nematodes, insects, mammals, and plants. SWI1, a member of the SWI/SNF protein complex that is involved in chromatin remodeling during transcription, contains the ARID motif. The ARID domain of human SWI1 (also known as p270) does not select for a specific DNA sequence from a random sequence pool. The lack of sequence specificity shown by the SWI1 ARID domain stands in contrast to the other characterized ARID domains, which recognize specific AT-rich sequences. We have solved the three-dimensional structure of human SWI1 ARID using solution NMR methods. In addition, we have characterized nonspecific DNA binding by the SWI1 ARID domain. Results from this study indicate that a flexible, long, internal loop in the ARID motif is likely to be important for sequence-specific DNA recognition. The structure of the human SWI1 ARID domain also represents a distinct structural subfamily. Studies of ARID indicate that the boundary of DNA binding structural and functional domains can extend beyond the sequence homologous region in a homologous family of proteins. Structural studies of homologous domains such as the ARID family of DNA-binding domains should provide information to better predict the boundary of structural and functional domains in structural genomic studies.

Amino Acid Sequence↗

PubMed2004

Solution structure of the C-terminal domain of Ku80 suggests important sites for protein-protein interactions.

The solution structure of Ku80 CTD from residue 566 to 732 has been solved in order to gain insights into the mechanisms of its interactions with other proteins. The structure reveals a topology similar to several common scaffolds for protein-protein interactions, in the absence of significant sequence similarity to these proteins. Conserved surface amino acid residues are clustered on two main surface areas, which are likely involved in mediating interactions between Ku80 and other proteins. The Ku70/Ku80 heterodimer has been shown to be involved in at least three processes, nonhomologous end joining, transcription, and telomere maintenance, and thus it needs to interact with different proteins involved in these different processes. The three-dimensional structure of the Ku80 C-terminal domain and the availability of NMR chemical shift assignments provide a basis for further investigation of the interactions between Ku80 and other proteins in these Ku-dependent cellular functions.

Alkyl and Aryl Transferases↗

PubMed2003

A high sensitivity 3D experiment for measuring Calpha-Halpha residual dipolar coupling constants.

A new sensitivity improved approach is presented to measure the Calpha-Halpha scalar and dipolar coupling constants in 13C/15N-labeled proteins using a HA(CA)CONH scheme. The proposed experiment has significantly higher sensitivity than the previously published (HA)CA(CO)NH sequence, and provides accurate and straightforward measurements of the scalar and residual dipolar coupling constants. The sequence is easy to implement, and has been demonstrated on the C-terminal domain of the human Ku-80 protein (152 amino acid residues). On average, sensitivity is improved by 40% for both isotropic and anisotropic samples. The sensitivity enhancement is more pronounced for structured regions than unstructured regions, with an average of 50-60% enhancement being observed in the well-structured regions of the protein.

Algorithms↗

PubMed2003

[Morphology of olfactory bulb, olfactory tract blood supply affected by anthrosclersis and its clinical significance].

OBJECTIVE: In order to provide morphological evidences for olfactory defect cased by olfactory bulb, olfactory tract ischemia, the origins, numbers, distributions and pathological changes about olfactory bulb, olfactory tract arteries were studied. METHOD: The distributions and pathological changes of olfactory bulb, olfactory tract arteries in 80 sides of adult brain specimens were observed with operation microscope, among which the nourishing arteries and nerve of olfactory tract in two sides aged from 60 to 70 were observed pathohistologically. RESULT: The blood supply of olfactory bulb, olfactory tract comes mainly form artery cerebral and posterior communicainy. 10% of these 60 sides arteries were of multi-branch. 86.3% of them had atheroselerosis. 25.0% of the olfactory bulb and olfactory tract artery were blocked or narrow, and pathological changes in olfactory nerve such as atrophy were observed. CONCLUSION: Excluding other diseases, the olfactory defect in different degree of patients over 60 years old were caused possibly by atheroselerosis of the arteries at base of the brain.

Adult↗