Professional Education

  • Doctor of Philosophy, University of Cambridge (2013)
  • Bachelor of Technology, Vellore Institute Technology (2008)

Stanford Advisors


All Publications

  • Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region. Nature Venkatakrishnan, A. J., Deupi, X., Lebon, G., Heydenreich, F. M., Flock, T., Miljus, T., Balaji, S., Bouvier, M., Veprintsev, D. B., Tate, C. G., Schertler, G. F., Babu, M. M. 2016; 536 (7617): 484-487

    View details for PubMedID 27525504

  • Structural insights into mu-opioid receptor activation NATURE Huang, W., Manglik, A., Venkatakrishnan, A. J., Laeremans, T., Feinberg, E. N., Sanborn, A. L., Kato, H. E., Livingston, K. E., Thorsen, T. S., Kling, R. C., Granier, S., Gmeiner, P., Husbands, S. M., Traynor, J. R., Weis, W. I., Steyaert, J., Dror, R. O., Kobilka, B. K. 2015; 524 (7565): 315-?
  • Structural insights into µ-opioid receptor activation. Nature Huang, W., Manglik, A., Venkatakrishnan, A. J., Laeremans, T., Feinberg, E. N., Sanborn, A. L., Kato, H. E., Livingston, K. E., Thorsen, T. S., Kling, R. C., Granier, S., Gmeiner, P., Husbands, S. M., Traynor, J. R., Weis, W. I., Steyaert, J., Dror, R. O., Kobilka, B. K. 2015; 524 (7565): 315-321


    Activation of the μ-opioid receptor (μOR) is responsible for the efficacy of the most effective analgesics. To shed light on the structural basis for μOR activation, here we report a 2.1 Å X-ray crystal structure of the murine μOR bound to the morphinan agonist BU72 and a G protein mimetic camelid antibody fragment. The BU72-stabilized changes in the μOR binding pocket are subtle and differ from those observed for agonist-bound structures of the β2-adrenergic receptor (β2AR) and the M2 muscarinic receptor. Comparison with active β2AR reveals a common rearrangement in the packing of three conserved amino acids in the core of the μOR, and molecular dynamics simulations illustrate how the ligand-binding pocket is conformationally linked to this conserved triad. Additionally, an extensive polar network between the ligand-binding pocket and the cytoplasmic domains appears to play a similar role in signal propagation for all three G-protein-coupled receptors.

    View details for DOI 10.1038/nature14886

    View details for PubMedID 26245379

  • Structural biology. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor. Science Burg, J. S., Ingram, J. R., Venkatakrishnan, A. J., Jude, K. M., Dukkipati, A., Feinberg, E. N., Angelini, A., Waghray, D., Dror, R. O., Ploegh, H. L., Garcia, K. C. 2015; 347 (6226): 1113-1117


    Chemokines are small proteins that function as immune modulators through activation of chemokine G protein-coupled receptors (GPCRs). Several viruses also encode chemokines and chemokine receptors to subvert the host immune response. How protein ligands activate GPCRs remains unknown. We report the crystal structure at 2.9 angstrom resolution of the human cytomegalovirus GPCR US28 in complex with the chemokine domain of human CX3CL1 (fractalkine). The globular body of CX3CL1 is perched on top of the US28 extracellular vestibule, whereas its amino terminus projects into the central core of US28. The transmembrane helices of US28 adopt an active-state-like conformation. Atomic-level simulations suggest that the agonist-independent activity of US28 may be due to an amino acid network evolved in the viral GPCR to destabilize the receptor's inactive state.

    View details for DOI 10.1126/science.aaa5026

    View details for PubMedID 25745166

  • Structured and disordered facets of the GPCR fold. Current opinion in structural biology Venkatakrishnan, A., Flock, T., Prado, D. E., Oates, M. E., Gough, J., Madan Babu, M. 2014; 27C: 129-137


    The seven-transmembrane (7TM) helix fold of G-protein coupled receptors (GPCRs) has been adapted for a wide variety of physiologically important signaling functions. Here, we discuss the diversity in the structured and disordered regions of GPCRs based on the recently published crystal structures and sequence analysis of all human GPCRs. A comparison of the structures of rhodopsin-like receptors (class A), secretin-like receptors (class B), metabotropic receptors (class C) and frizzled receptors (class F) shows that the relative arrangement of the transmembrane helices is conserved across all four GPCR classes although individual receptors can be activated by ligand binding at varying positions within and around the transmembrane helical bundle. A systematic analysis of GPCR sequences reveals the presence of disordered segments in the cytoplasmic side, abundant post-translational modification sites, evidence for alternative splicing and several putative linear peptide motifs that have the potential to mediate interactions with cytosolic proteins. While the structured regions permit the receptor to bind diverse ligands, the disordered regions appear to have an underappreciated role in modulating downstream signaling in response to the cellular state. An integrated paradigm combining the knowledge of structured and disordered regions is imperative for gaining a holistic understanding of the GPCR (un)structure-function relationship.

    View details for DOI 10.1016/

    View details for PubMedID 25198166

  • Molecular signatures of G-protein-coupled receptors NATURE Venkatakrishnan, A. J., Deupi, X., Lebon, G., Tate, C. G., Schertler, G. F., Babu, M. M. 2013; 494 (7436): 185-194


    G-protein-coupled receptors (GPCRs) are physiologically important membrane proteins that sense signalling molecules such as hormones and neurotransmitters, and are the targets of several prescribed drugs. Recent exciting developments are providing unprecedented insights into the structure and function of several medically important GPCRs. Here, through a systematic analysis of high-resolution GPCR structures, we uncover a conserved network of non-covalent contacts that defines the GPCR fold. Furthermore, our comparative analysis reveals characteristic features of ligand binding and conformational changes during receptor activation. A holistic understanding that integrates molecular and systems biology of GPCRs holds promise for new therapeutics and personalized medicine.

    View details for DOI 10.1038/nature11896

    View details for Web of Science ID 000315137700030

    View details for PubMedID 23407534

  • Deciphering membrane protein structures from protein sequences GENOME BIOLOGY Flock, T., Venkatakrishnan, A. J., Vinothkumar, K. R., Babu, M. M. 2012; 13 (6)


    Co-evolving positions within protein sequences have been used as spatial constraints to develop a computational approach for modeling membrane protein structures.

    View details for DOI 10.1186/gb-2012-13-6-160

    View details for Web of Science ID 000308546300012

    View details for PubMedID 22738306

  • Spial: analysis of subtype-specific features in multiple sequence alignments of proteins BIOINFORMATICS Wuster, A., Venkatakrishnan, A. J., Schertler, G. F., Babu, M. M. 2010; 26 (22): 2906-2907


    Spial (Specificity in alignments) is a tool for the comparative analysis of two alignments of evolutionarily related sequences that differ in their function, such as two receptor subtypes. It highlights functionally important residues that are either specific to one of the two alignments or conserved across both alignments. It permits visualization of this information in three complementary ways: by colour-coding alignment positions, by sequence logos and optionally by colour-coding the residues of a protein structure provided by the user. This can aid in the detection of residues that are involved in the subtype-specific interaction with a ligand, other proteins or nucleic acids. Spial may also be used to detect residues that may be post-translationally modified in one of the two sets of sequences.; supplementary information is available at

    View details for DOI 10.1093/bioinformatics/btq552

    View details for Web of Science ID 000283919800018

    View details for PubMedID 20880955

  • Homomeric protein complexes: evolution and assembly BIOCHEMICAL SOCIETY TRANSACTIONS Venkatakrishnan, A. J., Levy, E. D., Teichmann, S. A. 2010; 38: 879-882


    Homo-oligomeric protein complexes are functionally vital and highly abundant in living cells. In the present article, we review our current understanding of their geometry and evolution, including aspects of the symmetry of these complexes and their interaction interfaces. Also, we briefly discuss the pathway of their assembly in solution.

    View details for DOI 10.1042/BST0380879

    View details for Web of Science ID 000280753600004

    View details for PubMedID 20658970

  • MitoInteractome: Mitochondrial protein interactome database, and its application in 'aging network' analysis BMC GENOMICS Reja, R., Venkatakrishnan, A. J., Lee, J., Kim, B., Ryu, J., Gong, S., Bhak, J., Park, D. 2009; 10


    Mitochondria play a vital role in the energy production and apoptotic process of eukaryotic cells. Proteins in the mitochondria are encoded by nuclear and mitochondrial genes. Owing to a large increase in the number of identified mitochondrial protein sequences and completed mitochondrial genomes, it has become necessary to provide a web-based database of mitochondrial protein information.We present 'MitoInteractome', a consolidated web-based portal containing a wealth of information on predicted protein-protein interactions, physico-chemical properties, polymorphism, and diseases related to the mitochondrial proteome. MitoInteractome contains 6,549 protein sequences which were extracted from the following databases: SwissProt, MitoP, MitoProteome, HPRD and Gene Ontology database. The first general mitochondrial interactome has been constructed based on the concept of 'homologous interaction' using PSIMAP (Protein Structural Interactome MAP) and PEIMAP (Protein Experimental Interactome MAP). Using the above mentioned methods, protein-protein interactions were predicted for 74 species. The mitochondrial protein interaction data of humans was used to construct a network for the aging process. Analysis of the 'aging network' gave us vital insights into the interactions among proteins that influence the aging process.MitoInteractome is a comprehensive database that would (1) aid in increasing our understanding of the molecular functions and interaction networks of mitochondrial proteins, (2) help in identifying new target proteins for experimental research using predicted protein-protein interaction information, and (3) help in identifying biomarkers for diagnosis and new molecular targets for drug development related to mitochondria. MitoInteractome is available at

    View details for DOI 10.1186/1471-2164-10-S3-S20

    View details for Web of Science ID 000272356000020

    View details for PubMedID 19958484