About

Brenda Temple is an Adjunct Professor in the Department of Biochemistry and Biophysics at the University of North Carolina at Chapel Hill. Her research focuses on bioinformatics, molecular structural analysis, molecular dynamics simulations, molecular evolution, molecular modeling, and protein-protein interaction prediction. She has been recognized for her excellence in undergraduate teaching, receiving the Tanner Award for Excellence in Undergraduate Teaching in 2022.

Research topics

• Biology
• Neuroscience
• Genetics
• Immunology
• Cell biology
• Virology

Selected publications

• Laminin G domains define a critical interface for protein S-mediated factor IXa inhibition

  Journal of Thrombosis and Haemostasis · 2026-01-06

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  PublisherDOI

• Coro1A and TRIM67 collaborate in netrin-dependent neuronal morphogenesis

  The Journal of Cell Biology · 2025-10-14 · 1 citations

  article

  Neuronal morphogenesis depends on extracellular guidance cues accurately instructing intracellular cytoskeletal remodeling. Here, we describe a novel role of the actin binding protein coronin 1A (Coro1A) in neuronal morphogenesis, where it mediates responses to the axon guidance cue netrin-1. We found that Coro1A localizes to growth cones and filopodial structures and is required for netrin-dependent axon turning, branching, and corpus callosum development. We previously discovered that Coro1A interacts with TRIM67, a brain-enriched E3 ubiquitin ligase that binds the netrin receptor DCC, and is also required for netrin-mediated neuronal morphogenesis. Loss of Coro1A and loss of TRIM67 shared similar phenotypes, suggesting that they may function together in the same netrin pathway. A Coro1A mutant deficient in binding TRIM67 was unable to rescue loss of Coro1A phenotypes, indicating that the interaction between Coro1A and TRIM67 is required for netrin responses. Together, our findings reveal that Coro1A is required for proper neuronal morphogenesis, where it collaborates with TRIM67 downstream of netrin.

  PublisherDOI

• Functional conservation and divergence of the helix-turn-helix motif of E2 ubiquitin-conjugating enzymes

  UNC Libraries · 2024-08-14

  articleOpen access
  PublisherDOI

• Improvement of substrate specificity of the direct electron transfer type FAD-dependent glucose dehydrogenase catalytic subunit

  Journal of Biotechnology · 2024-09-25 · 4 citations

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  PublisherDOI

• Cdt1 variants reveal unanticipated aspects of interactions with cyclin/CDK and MCM important for normal genome replication

  UNC Libraries · 2024-07-09

  articleOpen accessSenior author

  The earliest step in DNA replication is origin licensing, which is the DNA loading of minichromosome maintenance (MCM) helicase complexes. The Cdc10-dependent transcript 1 (Cdt1) protein is essential for MCM loading during the G1 phase of the cell cycle, but the mechanism of Cdt1 function is still incompletely understood. We examined a collection of rare Cdt1 variants that cause a form of primordial dwarfism (the Meier-Gorlin syndrome) plus one hypomorphic Drosophila allele to shed light on Cdt1 function. Three hypomorphic variants load MCM less efficiently than wild-type (WT) Cdt1, and their lower activity correlates with impaired MCM binding. A structural homology model of the human Cdt1-MCM complex positions the altered Cdt1 residues at two distinct interfaces rather than the previously described single MCM interaction domain. Surprisingly, one dwarfism allele (Cdt1-A66T) is more active than WT Cdt1. This hypermorphic variant binds both cyclin A and SCFSkp2 poorly relative to WT Cdt1. Detailed quantitative live-cell imaging analysis demonstrated no change in the stability of this variant, however. Instead, we propose that cyclin A/CDK inhibits the Cdt1 licensing function independent of the creation of the SCFSkp2 phosphodegron. Together, these findings identify key Cdt1 interactions required for both efficient origin licensing and tight Cdt1 regulation to ensure normal cell proliferation and genome stability.

  PublisherDOI

• 2′3′-cGAMP interactome identifies 2′3′-cGAMP/Rab18/FosB signaling in cell migration control independent of innate immunity

  Science Advances · 2024-10-16 · 7 citations

  articleOpen access

  c-di-GAMP was first identified in bacteria to promote colonization, while mammalian 2′3′-cGAMP is synthesized by cGAS to activate STING for innate immune stimulation. However, 2′3′-cGAMP function beyond innate immunity remains elusive. Here, we report that 2′3′-cGAMP promotes cell migration independent of innate immunity. 2′3′-cGAMP interactome analysis identifies the small GTPase Rab18 as a 2′3′-cGAMP binding partner and effector in cell migration control. Mechanistically, 2′3′-cGAMP binds Rab18 to facilitate GTP loading and subsequent Rab18 activation, which further promotes FosB transcription in facilitating cell migration. Induced synthesis of endogenous 2′3′-cGAMP by intrabreast tumor bacterium S. aureus infection or low-dose doxorubicin treatment facilitates cell migration depending on the cGAS/cGAMP/Rab18/FosB signaling. We find that lovastatin induces Rab18 deprenylation that abolishes 2′3′-cGAMP recognition therefore suppressing cell migration. Together, our study reveals a previously unidentified 2′3′-cGAMP function in cell migration control via the 2′3′-cGAMP/Rab18/FosB signaling that provides additional insights into clinical applications of 2′3′-cGAMP.

  PublisherDOI

• The bromo-adjacent homology domains of PBRM1 associate with histone tails and contribute to PBAF-mediated gene regulation

  Journal of Biological Chemistry · 2023-06-30 · 4 citations

  articleOpen access

  A critical component of gene regulation is recognition of histones and their post-translational modifications by transcription-associated proteins or complexes. Although many histone-binding reader modules have been characterized, the bromo-adjacent homology (BAH) domain family of readers is still poorly characterized. A pre-eminent member of this family is PBRM1 (BAF180), a component of the PBAF chromatin-remodeling complex. PBRM1 contains two adjacent BAH domains of unknown histone-binding potential. We evaluated the tandem BAH domains for their capacity to associate with histones and to contribute to PBAF-mediated gene regulation. The BAH1 and BAH2 domains of human PBRM1 broadly interacted with histone tails, but they showed a preference for unmodified N-termini of histones H3 and H4. Molecular modeling and comparison of the BAH1 and BAH2 domains with other BAH readers pointed to a conserved binding mode via an extended open pocket and, in general, an aromatic cage for histone lysine binding. Point mutants that were predicted to disrupt the interaction between the BAH domains and histones reduced histone binding in vitro and resulted in dysregulation of genes targeted by PBAF in cellulo. Although the BAH domains in PBRM1 were important for PBAF-mediated gene regulation, we found that overall chromatin targeting of PBRM1 was not dependent on BAH-histone interaction. Our findings identify a function of the PBRM1 BAH domains in PBAF activity that is likely mediated by histone tail interaction.

  PublisherOA PDFDOI

• KSHV Viral Protein Kinase Interacts with USP9X to Modulate the Viral Lifecycle

  Journal of Virology · 2023-03-06 · 6 citations

  articleOpen access

  Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi sarcoma (KS), the plasmablastic form of multicentric Castleman's disease, and primary effusion lymphoma. In sub-Saharan Africa, KS is the most common HIV-related malignancy. KSHV encodes a viral protein kinase (vPK) that aids viral replication. To elucidate the interactions of vPK with cellular proteins in KSHV-infected cells, we used an affinity purification approach and identified host protein ubiquitin-specific peptidase 9X-linked (USP9X) as a potential interactor of vPK. Depletion of USP9X inhibits both viral reactivation and the production of infectious virions. Overall, our data suggest a proviral role for USP9X.

  PublisherOA PDFDOI

• Distinct developmental phenotypes result from mutation of Set8/KMT5A and histone H4 lysine 20 in <i>Drosophila melanogaster</i>

  Genetics · 2022-04-11 · 10 citations

  articleOpen access

  Mono-methylation of histone H4 lysine 20 (H4K20me1) is catalyzed by Set8/KMT5A and regulates numerous aspects of genome organization and function. Loss-of-function mutations in Drosophila melanogaster Set8 or mammalian KMT5A prevent H4K20me1 and disrupt development. Set8/KMT5A also has non-histone substrates, making it difficult to determine which developmental functions of Set8/KMT5A are attributable to H4K20me1 and which to other substrates or to non-catalytic roles. Here, we show that human KMT5A can functionally substitute for Set8 during Drosophila development and that the catalytic SET domains of the two enzymes are fully interchangeable. We also uncovered a role in eye development for the N-terminal domain of Set8 that cannot be complemented by human KMT5A. Whereas Set820/20 null mutants are inviable, we found that an R634G mutation in Set8 predicted from in vitro experiments to ablate catalytic activity resulted in viable adults. Additionally, Set8(R634G) mutants retain significant, albeit reduced, H4K20me1, indicating that the R634G mutation does not eliminate catalytic activity in vivo and is functionally hypomorphic rather than null. Flies engineered to express only unmodifiable H4 histones (H4K20A) can also complete development, but are phenotypically distinct from H4K20R, Set820/20 null, and Set8R634G mutants. Taken together, our results demonstrate functional conservation of KMT5A and Set8 enzymes, as well as distinct roles for Set8 and H4K20me1 in Drosophila development.

  PublisherOA PDFDOI

• Dynamics of allosteric regulation of the phospholipase C-γ isozymes upon recruitment to membranes

  eLife · 2022-05-23 · 18 citations

  articleOpen access

  Numerous receptor tyrosine kinases and immune receptors activate phospholipase C-γ (PLC-γ) isozymes at membranes to control diverse cellular processes including phagocytosis, migration, proliferation, and differentiation. The molecular details of this process are not well understood. Using hydrogen-deuterium exchange mass spectrometry, we show that PLC-γ1 is relatively inert to lipid vesicles that contain its substrate, phosphatidylinositol 4,5-bisphosphate (PIP 2 ), unless first bound to the kinase domain of the fibroblast growth factor receptor (FGFR1). Exchange occurs throughout PLC-γ1 and is exaggerated in PLC-γ1 containing an oncogenic substitution (D1165H) that allosterically activates the lipase. These data support a model whereby initial complex formation shifts the conformational equilibrium of PLC-γ1 to favor activation. This receptor-induced priming of PLC-γ1 also explains the capacity of a kinase-inactive fragment of FGFR1 to modestly enhance the lipase activity of PLC-γ1 operating on lipid vesicles but not a soluble analog of PIP 2 and highlights potential cooperativity between receptor engagement and membrane proximity. Priming is expected to be greatly enhanced for receptors embedded in membranes and nearly universal for the myriad of receptors and co-receptors that bind the PLC-γ isozymes.

  PublisherDOI

Recent grants

• Studies on Agrocin 84-a "Trojan Horse" tRNA synthetase inhibitor

  NSF · $876k · 2012–2018

Frequent coauthors

• Stephen G. Chaney

  University of North Carolina at Chapel Hill

  25 shared

• Nikolay V. Dokholyan

  Hershey (United States)

  22 shared

• Alan M. Jones

  University of Illinois Urbana-Champaign

  21 shared

• Sharon L. Campbell

  Rutgers, The State University of New Jersey

  19 shared

• John Sondek

  University of North Carolina at Chapel Hill

  15 shared

• Yibing Wu

  University of California, San Francisco

  13 shared

• Debadeep Bhattacharyya

  Covaris (United States)

  13 shared

• Andrés Palencia

  Université Grenoble Alpes

  11 shared

Labs

• Biochemistry and BiophysicsPI

Awards & honors

• 2022 Tanner Award for Excellence in Undergraduate Teaching (…